Variant chr17-81510498-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001614.5(ACTG1):c.*192G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 779,208 control chromosomes in the GnomAD database, including 426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 223 hom., cov: 32)

Exomes 𝑓: 0.018 ( 203 hom. )

Consequence

ACTG1
NM_001614.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.80

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=-0.64).

BP6

Variant 17-81510498-C-G is Benign according to our data. Variant chr17-81510498-C-G is described in ClinVar as [Benign]. Clinvar id is 1268147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ACTG1	NM_001614.5 linkuse as main transcript	c.*192G>C	3_prime_UTR_variant	6/6	ENST00000573283.7
ACTG1	NM_001199954.3 linkuse as main transcript	c.*192G>C	3_prime_UTR_variant	6/6
ACTG1	NR_037688.3 linkuse as main transcript	n.1392G>C	non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG1	ENST00000573283.7 linkuse as main transcript	c.*192G>C		3_prime_UTR_variant	6/6	5	NM_001614.5	P4

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6126

AN:

152170

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.0331

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0412

GnomAD3 exomes

AF:

0.0223

AC:

3248

AN:

145614

Hom.:

AF XY:

0.0209

AC XY:

1649

AN XY:

78776

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0205

Gnomad ASJ exome

AF:

0.0479

Gnomad EAS exome

AF:

0.0297

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.00499

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0208

GnomAD4 exome

AF:

0.0175

AC:

10975

AN:

626920

Hom.:

203

Cov.:

AF XY:

0.0169

AC XY:

5665

AN XY:

334630

show subpopulations

Gnomad4 AFR exome

AF:

0.0936

Gnomad4 AMR exome

AF:

0.0206

Gnomad4 ASJ exome

AF:

0.0491

Gnomad4 EAS exome

AF:

0.0206

Gnomad4 SAS exome

AF:

0.0166

Gnomad4 FIN exome

AF:

0.00534

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0253

GnomAD4 genome

AF:

0.0403

AC:

6135

AN:

152288

Hom.:

223

Cov.:

AF XY:

0.0399

AC XY:

2970

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.0329

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0280

Hom.:

Bravo

AF:

0.0439

Asia WGS

AF:

0.0400

AC:

137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.77

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