rs771128098

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_015404.4(WHRN):c.75C>T(p.Gly25Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,504,420 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00089 ( 2 hom., cov: 34)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

WHRN
NM_015404.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.279

Publications

0 publications found

Variant links:

Genes affected

WHRN (HGNC:16361): (whirlin) This gene is thought to function in the organization and stabilization of sterocilia elongation and actin cystoskeletal assembly, based on studies of the related mouse gene. Mutations in this gene have been associated with autosomal recessive non-syndromic deafness and Usher Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

WHRN Gene-Disease associations (from GenCC):

Usher syndrome type 2D
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
autosomal recessive nonsyndromic hearing loss 31
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Usher syndrome type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WHRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 9-114504727-G-A is Benign according to our data. Variant chr9-114504727-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.279 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000893 (136/152234) while in subpopulation AFR AF = 0.0032 (133/41558). AF 95% confidence interval is 0.00276. There are 2 homozygotes in GnomAd4. There are 70 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WHRN	NM_015404.4 link	c.75C>T	p.Gly25Gly	synonymous_variant	Exon 1 of 12	ENST00000362057.4	NP_056219.3	Q9P202-1B9EGE6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4 link	c.75C>T	p.Gly25Gly	synonymous_variant	Exon 1 of 12	1	NM_015404.4	ENSP00000354623.3		Q9P202-1

Frequencies

GnomAD3 genomes

AF:

0.000894

AC:

136

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000101

AC:

AN:

99252

AF XY:

0.000127

show subpopulations

Gnomad AFR exome

AF:

0.00337

Gnomad AMR exome

AF:

0.0000502

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000769

AC:

104

AN:

1352186

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

666424

show subpopulations

African (AFR)

AF:

0.00324

AC:

AN:

28074

American (AMR)

AF:

0.0000321

AC:

AN:

31114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22898

East Asian (EAS)

AF:

0.00

AC:

AN:

33218

South Asian (SAS)

AF:

0.00

AC:

AN:

74044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34416

Middle Eastern (MID)

AF:

0.000250

AC:

AN:

4000

European-Non Finnish (NFE)

AF:

0.00000281

AC:

AN:

1068026

Other (OTH)

AF:

0.000142

AC:

AN:

56396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000893

AC:

136

AN:

152234

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00320

AC:

133

AN:

41558

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.000475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000895

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 07, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 22, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Gly25Gly in exon 1 of DFNB31: 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 0.3% (39/11234) of A frican chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs771128098). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.28

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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rs771128098

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