9-114426434-T-C

Variant names:

Variant summary

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

The NM_015404.4(WHRN):c.964-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,612,952 control chromosomes in the GnomAD database, including 74,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7470 hom., cov: 33)

Exomes 𝑓: 0.30 ( 67272 hom. )

Consequence

WHRN
NM_015404.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.643

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-114426434-T-C is Benign according to our data. Variant chr9-114426434-T-C is described in ClinVar as Benign. ClinVar VariationId is 1238923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015404.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WHRN	NM_015404.4	MANE Select	c.964-21A>G	intron	N/A	NP_056219.3
WHRN	NM_001173425.2		c.964-21A>G	intron	N/A	NP_001166896.1
WHRN	NM_001083885.3		c.-186-21A>G	intron	N/A	NP_001077354.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WHRN	ENST00000362057.4	TSL:1 MANE Select	c.964-21A>G	intron	N/A	ENSP00000354623.3
WHRN	ENST00000265134.10	TSL:1	c.-186-21A>G	intron	N/A	ENSP00000265134.6
WHRN	ENST00000674036.9		c.964-21A>G	intron	N/A	ENSP00000501297.5

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47540

AN:

151868

Hom.:

7449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.320

GnomAD2 exomes

AF:

0.330

AC:

81254

AN:

246114

AF XY:

0.323

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.468

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.300

AC:

438246

AN:

1460966

Hom.:

67272

Cov.:

AF XY:

0.300

AC XY:

218253

AN XY:

726756

show subpopulations

African (AFR)

AF:

0.332

AC:

11117

AN:

33472

American (AMR)

AF:

0.457

AC:

20423

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

7428

AN:

26136

East Asian (EAS)

AF:

0.401

AC:

15918

AN:

39696

South Asian (SAS)

AF:

0.352

AC:

30388

AN:

86224

European-Finnish (FIN)

AF:

0.286

AC:

15156

AN:

53018

Middle Eastern (MID)

AF:

0.290

AC:

1648

AN:

5686

European-Non Finnish (NFE)

AF:

0.286

AC:

317823

AN:

1111658

Other (OTH)

AF:

0.304

AC:

18345

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

17462

34924

52385

69847

87309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10818

21636

32454

43272

54090

<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:

0.313

AC:

47611

AN:

151986

Hom.:

7470

Cov.:

AF XY:

0.313

AC XY:

23281

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.333

AC:

13805

AN:

41432

American (AMR)

AF:

0.370

AC:

5658

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1048

AN:

3468

East Asian (EAS)

AF:

0.374

AC:

1929

AN:

5162

South Asian (SAS)

AF:

0.346

AC:

1671

AN:

4824

European-Finnish (FIN)

AF:

0.290

AC:

3063

AN:

10574

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19433

AN:

67934

Other (OTH)

AF:

0.317

AC:

669

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1692

3384

5077

6769

8461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.307

Hom.:

4143

Bravo

AF:

0.323

Asia WGS

AF:

0.332

AC:

1155

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jun 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Autosomal recessive nonsyndromic hearing loss 31

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

8.8

(source)

DANN

Benign

0.76

PhyloP100

-0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over