Variant 15-43607955-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153700.2(STRC):c.3702G>A(p.Glu1234=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,608,708 control chromosomes in the GnomAD database, including 28,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2535 hom., cov: 22)

Exomes 𝑓: 0.17 ( 25578 hom. )

Consequence

STRC
NM_153700.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.659

Variant links:

Genes affected

STRC (HGNC:16035): (stereocilin) This gene encodes a protein that is associated with the hair bundle of the sensory hair cells in the inner ear. The hair bundle is composed of stiff microvilli called stereocilia and is involved with mechanoreception of sound waves. This gene is part of a tandem duplication on chromosome 15; the second copy is a pseudogene. Mutations in this gene cause autosomal recessive non-syndromic deafness. [provided by RefSeq, Jul 2008]

STRC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 15-43607955-C-T is Benign according to our data. Variant chr15-43607955-C-T is described in ClinVar as [Benign]. Clinvar id is 165313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43607955-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.659 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRC	NM_153700.2 linkuse as main transcript	c.3702G>A	p.Glu1234=	synonymous_variant	18/29	ENST00000450892.7	NP_714544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7 linkuse as main transcript	c.3702G>A	p.Glu1234=	synonymous_variant	18/29	5	NM_153700.2	ENSP00000401513	P2

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23036

AN:

148428

Hom.:

2525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.00137

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.165

GnomAD3 exomes

AF:

0.147

AC:

36858

AN:

250804

Hom.:

3842

AF XY:

0.152

AC XY:

20654

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.0972

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.00245

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.168

AC:

245812

AN:

1460164

Hom.:

25578

Cov.:

AF XY:

0.169

AC XY:

123111

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.155

AC:

23070

AN:

148544

Hom.:

2535

Cov.:

AF XY:

0.152

AC XY:

11006

AN XY:

72580

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.00137

Gnomad4 SAS

AF:

0.153

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.172

Hom.:

511

Bravo

AF:

0.156

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Glu1234Glu in Exon 18 of STRC: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 18.4% (1291/7014) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs150548868). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.2

DANN

Benign

0.79

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