17-81511890-G-T

Variant names:

Variant summary

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

The NM_001614.5(ACTG1):c.363+13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,613,646 control chromosomes in the GnomAD database, including 171,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15748 hom., cov: 33)

Exomes 𝑓: 0.45 ( 155388 hom. )

Consequence

ACTG1
NM_001614.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.936

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-81511890-G-T is Benign according to our data. Variant chr17-81511890-G-T is described in ClinVar as [Benign]. Clinvar id is 44147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81511890-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ACTG1	NM_001614.5 link	c.363+13C>A	intron_variant	Intron 3 of 5	ENST00000573283.7	NP_001605.1	P63261
ACTG1	NM_001199954.3 link	c.363+13C>A	intron_variant	Intron 3 of 5		NP_001186883.1	P63261
ACTG1	NR_037688.3 link	n.435+13C>A	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTG1	ENST00000573283.7 link	c.363+13C>A		intron_variant	Intron 3 of 5	5	NM_001614.5	ENSP00000458435.1		P63261

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68121

AN:

151982

Hom.:

15728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.455

GnomAD3 exomes

AF:

0.498

AC:

124455

AN:

250080

Hom.:

33035

AF XY:

0.501

AC XY:

67961

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.505

Gnomad ASJ exome

AF:

0.469

Gnomad EAS exome

AF:

0.875

Gnomad SAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.435

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.453

AC:

662233

AN:

1461546

Hom.:

155388

Cov.:

AF XY:

0.459

AC XY:

333405

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.400

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.468

Gnomad4 EAS exome

AF:

0.820

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.423

Gnomad4 NFE exome

AF:

0.427

Gnomad4 OTH exome

AF:

0.466

GnomAD4 genome

AF:

0.448

AC:

68176

AN:

152100

Hom.:

15748

Cov.:

AF XY:

0.454

AC XY:

33724

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.399

Gnomad4 AMR

AF:

0.471

Gnomad4 ASJ

AF:

0.470

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.629

Gnomad4 FIN

AF:

0.419

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.462

Alfa

AF:

0.436

Hom.:

16265

Bravo

AF:

0.452

Asia WGS

AF:

0.695

AC:

2417

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Mar 07, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

363+13C>A in Intron 03 of ACTG1: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 43.2% (3019/6996) of European American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs9910792). -

Oct 15, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 20

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Baraitser-winter syndrome 2

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 20;C3281235:Baraitser-winter syndrome 2

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

-0.85

CADD

Benign

0.013

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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