17-81511224-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001614.5(ACTG1):c.766C>A(p.Arg256Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ACTG1
NM_001614.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05

Publications

11 publications found

Variant links:

Genes affected

ACTG1 (HGNC:144): (actin gamma 1) Actins are highly conserved proteins that are involved in various types of cell motility and in maintenance of the cytoskeleton. Three main groups of actin isoforms have been identified in vertebrate animals: alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. Actin gamma 1, encoded by this gene, is a cytoplasmic actin found in all cell types. Mutations in this gene are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss and also with Baraitser-Winter syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACTG1 Gene-Disease associations (from GenCC):

Baraitser-winter syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss 20
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Baraitser-Winter cerebrofrontofacial syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACTG1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 17-81511224-G-T is Benign according to our data. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-81511224-G-T is described in CliVar as Likely_benign. Clinvar id is 748623.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000123 (18/1461396) while in subpopulation EAS AF = 0.000403 (16/39700). AF 95% confidence interval is 0.000252. There are 0 homozygotes in GnomAdExome4. There are 7 alleles in the male GnomAdExome4 subpopulation. Median coverage is 37. This position passed quality control check.

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTG1	NM_001614.5 link	c.766C>A	p.Arg256Arg	synonymous_variant	Exon 4 of 6	ENST00000573283.7	NP_001605.1	P63261
ACTG1	NM_001199954.3 link	c.766C>A	p.Arg256Arg	synonymous_variant	Exon 4 of 6		NP_001186883.1	P63261
ACTG1	NR_037688.3 link	n.838C>A		non_coding_transcript_exon_variant	Exon 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTG1	ENST00000573283.7 link	c.766C>A	p.Arg256Arg	synonymous_variant	Exon 4 of 6	5	NM_001614.5	ENSP00000458435.1		P63261

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250764

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461396

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000403

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112004

Other (OTH)

AF:

0.0000166

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over