rs10513247

Variant names:

• chr9-114468911-T-C
• rs10513247
• NM_015404.4:c.838-2519A>G

Variant summary

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

The NM_015404.4(WHRN):​c.838-2519A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,088 control chromosomes in the GnomAD database, including 6,377 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 0.28 (6377 hom., cov: 32)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WHRN	NM_015404.4	c.838-2519A>G		intron_variant	Intron 2 of 11	ENST00000362057.4	NP_056219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4	c.838-2519A>G		intron_variant	Intron 2 of 11	1	NM_015404.4	ENSP00000354623.3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43074 AN: 151970 Hom.: 6362 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.284 AC: 43126 AN: 152088 Hom.: 6377 Cov.: 32 AF XY: 0.287 AC XY: 21323 AN XY: 74316

African (AFR) AF: 0.296 AC: 12285 AN: 41498

American (AMR) AF: 0.359 AC: 5490 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1715 AN: 5140

South Asian (SAS) AF: 0.344 AC: 1662 AN: 4832

European-Finnish (FIN) AF: 0.313 AC: 3307 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17070 AN: 67980

Other (OTH) AF: 0.258 AC: 544 AN: 2112

Alfa AF: 0.259 Hom.: 649

Bravo AF: 0.287

Asia WGS AF: 0.283 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.2
DANN	Benign	0.76
PhyloP100		0.18
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: rs10513247; hg19: chr9-117231191;