rs11549220

Positions:

chr17-81512089-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001614.5(ACTG1):c.177G>A(p.Gln59=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0185 in 1,613,906 control chromosomes in the GnomAD database, including 480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 23 hom., cov: 32)

Exomes 𝑓: 0.019 ( 457 hom. )

Consequence

ACTG1
NM_001614.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.81

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 17-81512089-C-T is Benign according to our data. Variant chr17-81512089-C-T is described in ClinVar as [Benign]. Clinvar id is 44146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81512089-C-T is described in Lovd as [Likely_benign]. Variant chr17-81512089-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACTG1	NM_001614.5 linkuse as main transcript	c.177G>A	p.Gln59=	synonymous_variant	3/6	ENST00000573283.7
ACTG1	NM_001199954.3 linkuse as main transcript	c.177G>A	p.Gln59=	synonymous_variant	3/6
ACTG1	NR_037688.3 linkuse as main transcript	n.249G>A		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG1	ENST00000573283.7 linkuse as main transcript	c.177G>A	p.Gln59=	synonymous_variant	3/6	5	NM_001614.5	P4

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2051

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00306

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.0274

Gnomad SAS

AF:

0.0609

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0235

AC:

5910

AN:

250980

Hom.:

116

AF XY:

0.0245

AC XY:

3326

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00310

Gnomad AMR exome

AF:

0.0362

Gnomad ASJ exome

AF:

0.00825

Gnomad EAS exome

AF:

0.0213

Gnomad SAS exome

AF:

0.0615

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.0154

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0190

AC:

27825

AN:

1461580

Hom.:

457

Cov.:

AF XY:

0.0201

AC XY:

14580

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.0333

Gnomad4 ASJ exome

AF:

0.00704

Gnomad4 EAS exome

AF:

0.0531

Gnomad4 SAS exome

AF:

0.0571

Gnomad4 FIN exome

AF:

0.0155

Gnomad4 NFE exome

AF:

0.0153

Gnomad4 OTH exome

AF:

0.0180

GnomAD4 genome

AF:

0.0135

AC:

2054

AN:

152326

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1050

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00305

Gnomad4 AMR

AF:

0.0225

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.0276

Gnomad4 SAS

AF:

0.0608

Gnomad4 FIN

AF:

0.0163

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.0540

AC:

187

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0155

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Gln59Gln in Exon 03 of ACTG1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1.5% (105/7020) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs11549220). -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 09, 2015	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. -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 30, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nonsyndromic hearing loss 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Baraitser-winter syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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