rs2920780

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153700.2(STRC):c.3893A>G(p.His1298Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,590,212 control chromosomes in the GnomAD database, including 21,538 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5826 hom., cov: 30)

Exomes 𝑓: 0.12 ( 15712 hom. )

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.35

Publications

20 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021159947).

BP6

Variant 15-43605301-T-C is Benign according to our data. Variant chr15-43605301-T-C is described in ClinVar as Benign. ClinVar VariationId is 165312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.3893A>G	p.His1298Arg	missense_variant	Exon 19 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.3893A>G	p.His1298Arg	missense_variant	Exon 19 of 29	5	NM_153700.2	ENSP00000401513.2		Q7RTU9

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32808

AN:

151178

Hom.:

5814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.0941

Gnomad OTH

AF:

0.191

GnomAD2 exomes

AF:

0.161

AC:

32392

AN:

200968

AF XY:

0.154

show subpopulations

Gnomad AFR exome

AF:

0.477

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.0391

Gnomad NFE exome

AF:

0.0978

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.120

AC:

172233

AN:

1438918

Hom.:

15712

Cov.:

AF XY:

0.120

AC XY:

85682

AN XY:

713602

show subpopulations

African (AFR)

AF:

0.501

AC:

16632

AN:

33182

American (AMR)

AF:

0.199

AC:

8160

AN:

40984

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

4817

AN:

25652

East Asian (EAS)

AF:

0.274

AC:

10711

AN:

39088

South Asian (SAS)

AF:

0.175

AC:

14580

AN:

83200

European-Finnish (FIN)

AF:

0.0401

AC:

2084

AN:

51980

Middle Eastern (MID)

AF:

0.134

AC:

760

AN:

5686

European-Non Finnish (NFE)

AF:

0.0963

AC:

105933

AN:

1099614

Other (OTH)

AF:

0.144

AC:

8556

AN:

59532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9426

18853

28279

37706

47132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4300

8600

12900

17200

21500

<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:

0.217

AC:

32866

AN:

151294

Hom.:

5826

Cov.:

AF XY:

0.214

AC XY:

15799

AN XY:

73916

show subpopulations

African (AFR)

AF:

0.477

AC:

19613

AN:

41086

American (AMR)

AF:

0.195

AC:

2960

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

628

AN:

3458

East Asian (EAS)

AF:

0.273

AC:

1394

AN:

5108

South Asian (SAS)

AF:

0.192

AC:

912

AN:

4760

European-Finnish (FIN)

AF:

0.0402

AC:

424

AN:

10542

Middle Eastern (MID)

AF:

0.175

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0940

AC:

6380

AN:

67844

Other (OTH)

AF:

0.194

AC:

407

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

983

1966

2948

3931

4914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.171

Hom.:

719

Bravo

AF:

0.245

ESP6500AA

AF:

0.451

AC:

1981

ESP6500EA

AF:

0.0978

AC:

836

ExAC

AF:

0.147

AC:

17652

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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. -

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

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

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

His1298Arg in Exon 19 of STRC: This variant is not expected to have clinical sig nificance because it has been identified in 44.6% (1663/3728) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs2920780). -

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

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

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.93

PhyloP100

1.3

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.098

Sift

Benign

0.22

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0

B;B

Vest4

0.13

ClinPred

0.0040

GERP RS

2.9

Varity_R

0.054

gMVP

0.39

Mutation Taster

=98/2

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