rs62018890

chr15-43607955-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.659

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]

ACMG classification

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	UniProt
STRC	NM_153700.2	c.3702G>A	p.Glu1234=	synonymous_variant	18/29	ENST00000450892.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23036 AN: 148428 Hom.: 2525 Cov.: 22

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

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.: 33 AF XY: 0.169 AC XY: 123111 AN XY: 726476

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.: 22 AF XY: 0.152 AC XY: 11006 AN XY: 72580

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:3

Revision: criteria provided, multiple submitters, no conflicts

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). -

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

Other links and lift over

dbSNP: rs62018890; hg19: chr15-43900153; COSMIC: COSV68659796; COSMIC: COSV68659796;