rs11787667

Variant names:

• chr9-114480565-C-T
• rs11787667
• NM_015404.4:c.619-1794G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015404.4(WHRN):​c.619-1794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,884 control chromosomes in the GnomAD database, including 13,938 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13938 hom., cov: 31)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WHRN	NM_015404.4	c.619-1794G>A		intron_variant	Intron 1 of 11	ENST00000362057.4	NP_056219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4	c.619-1794G>A		intron_variant	Intron 1 of 11	1	NM_015404.4	ENSP00000354623.3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59065 AN: 151766 Hom.: 13937 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.429

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.389 AC: 59066 AN: 151884 Hom.: 13938 Cov.: 31 AF XY: 0.386 AC XY: 28648 AN XY: 74212

African (AFR) AF: 0.113 AC: 4685 AN: 41462

American (AMR) AF: 0.390 AC: 5953 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1561 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3002 AN: 5146

South Asian (SAS) AF: 0.526 AC: 2527 AN: 4802

European-Finnish (FIN) AF: 0.381 AC: 4009 AN: 10528

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35749 AN: 67912

Other (OTH) AF: 0.431 AC: 909 AN: 2110

Alfa AF: 0.432 Hom.: 2680

Bravo AF: 0.377

Asia WGS AF: 0.515 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.76
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11787667; hg19: chr9-117242845; COSMIC: COSV54329067;