Variant chr17-81510431-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001614.5(ACTG1):c.*259C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 598,602 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: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

ACTG1
NM_001614.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.26

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-81510431-G-A is Benign according to our data. Variant chr17-81510431-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1189483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000263 (40/152308) while in subpopulation NFE AF= 0.000294 (20/68036). AF 95% confidence interval is 0.000194. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ACTG1	NM_001614.5 linkuse as main transcript	c.*259C>T	3_prime_UTR_variant	6/6	ENST00000573283.7
ACTG1	NM_001199954.3 linkuse as main transcript	c.*259C>T	3_prime_UTR_variant	6/6
ACTG1	NR_037688.3 linkuse as main transcript	n.1411+48C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG1	ENST00000573283.7 linkuse as main transcript	c.*259C>T		3_prime_UTR_variant	6/6	5	NM_001614.5	P4

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000401

AC:

AN:

122056

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

65534

show subpopulations

Gnomad AFR exome

AF:

0.000471

Gnomad AMR exome

AF:

0.000523

Gnomad ASJ exome

AF:

0.000910

Gnomad EAS exome

AF:

0.0000951

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.000238

Gnomad NFE exome

AF:

0.000428

Gnomad OTH exome

AF:

0.000807

GnomAD4 exome

AF:

0.000309

AC:

138

AN:

446294

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

241160

show subpopulations

Gnomad4 AFR exome

AF:

0.000532

Gnomad4 AMR exome

AF:

0.000502

Gnomad4 ASJ exome

AF:

0.000511

Gnomad4 EAS exome

AF:

0.0000864

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000431

Gnomad4 NFE exome

AF:

0.000314

Gnomad4 OTH exome

AF:

0.000582

GnomAD4 genome

AF:

0.000263

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000355

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 07, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.5

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over