rs62018890

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153700.2(STRC):c.3702G>A(p.Glu1234Glu) 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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 16
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

STRC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 165313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.3702G>A	p.Glu1234Glu	synonymous_variant	Exon 18 of 29	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7 link	c.3702G>A	p.Glu1234Glu	synonymous_variant	Exon 18 of 29	5	NM_153700.2	ENSP00000401513.2		Q7RTU9

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

GnomAD2 exomes

AF:

0.147

AC:

36858

AN:

250804

AF XY:

0.152

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 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

African (AFR)

AF:

0.156

AC:

5136

AN:

32910

American (AMR)

AF:

0.101

AC:

4525

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5193

AN:

26094

East Asian (EAS)

AF:

0.00134

AC:

AN:

39634

South Asian (SAS)

AF:

0.181

AC:

15639

AN:

86210

European-Finnish (FIN)

AF:

0.110

AC:

5848

AN:

53388

Middle Eastern (MID)

AF:

0.248

AC:

1428

AN:

5752

European-Non Finnish (NFE)

AF:

0.178

AC:

197923

AN:

1111170

Other (OTH)

AF:

0.167

AC:

10067

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

12607

25214

37820

50427

63034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6770

13540

20310

27080

33850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.155

AC:

23070

AN:

148544

Hom.:

2535

Cov.:

AF XY:

0.152

AC XY:

11006

AN XY:

72580

show subpopulations

African (AFR)

AF:

0.156

AC:

6048

AN:

38816

American (AMR)

AF:

0.140

AC:

2108

AN:

15040

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

669

AN:

3438

East Asian (EAS)

AF:

0.00137

AC:

AN:

5116

South Asian (SAS)

AF:

0.153

AC:

728

AN:

4758

European-Finnish (FIN)

AF:

0.103

AC:

1079

AN:

10426

Middle Eastern (MID)

AF:

0.253

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.176

AC:

11913

AN:

67676

Other (OTH)

AF:

0.163

AC:

337

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

819

1637

2456

3274

4093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

May 09, 2017

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. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Jul 15, 2021

Genome-Nilou Lab

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

-0.47

CADD

Benign

5.2

(source)

DANN

Benign

0.79

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over