rs10739410

Variant names:

• chr9-114403754-T-C
• rs10739410
• NM_015404.4:c.2418+142A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-114403754-T-C
• chr9-114403754-T-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015404.4(WHRN):​c.2418+142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,069,302 control chromosomes in the GnomAD database, including 123,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14100 hom., cov: 33)
  • Exomes 𝑓: 0.48 (109515 hom.)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.657
• 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, Unknown Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P
• autosomal recessive nonsyndromic hearing loss 31

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-114403754-T-C is Benign according to our data. Variant chr9-114403754-T-C is described in ClinVar as Benign. ClinVar VariationId is 678779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WHRN	NM_015404.4	MANE Select	c.2418+142A>G		intron	N/A	NP_056219.3	Q9P202-1
	WHRN	NM_001173425.2		c.2415+142A>G		intron	N/A	NP_001166896.1
	WHRN	NM_001346890.1		c.1365+142A>G		intron	N/A	NP_001333819.1	Q9P202-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WHRN	ENST00000362057.4	TSL:1 MANE Select	c.2418+142A>G		intron	N/A	ENSP00000354623.3	Q9P202-1
	WHRN	ENST00000265134.10	TSL:1	c.1269+142A>G		intron	N/A	ENSP00000265134.6	Q9P202-3
	WHRN	ENST00000866780.1		c.2415+142A>G		intron	N/A	ENSP00000536839.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62975 AN: 151998 Hom.: 14093 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.450

GnomAD4 exome AF: 0.485 AC: 444472 AN: 917184 Hom.: 109515 AF XY: 0.489 AC XY: 232986 AN XY: 476834

African (AFR) AF: 0.211 AC: 4893 AN: 23214

American (AMR) AF: 0.485 AC: 20065 AN: 41372

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 13215 AN: 22330

East Asian (EAS) AF: 0.505 AC: 18153 AN: 35958

South Asian (SAS) AF: 0.536 AC: 39349 AN: 73356

European-Finnish (FIN) AF: 0.475 AC: 17723 AN: 37336

Middle Eastern (MID) AF: 0.564 AC: 1776 AN: 3150

European-Non Finnish (NFE) AF: 0.485 AC: 309181 AN: 637816

Other (OTH) AF: 0.472 AC: 20117 AN: 42652

GnomAD4 genome AF: 0.414 AC: 62999 AN: 152118 Hom.: 14100 Cov.: 33 AF XY: 0.414 AC XY: 30753 AN XY: 74364

African (AFR) AF: 0.220 AC: 9149 AN: 41518

American (AMR) AF: 0.449 AC: 6862 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2085 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2418 AN: 5158

South Asian (SAS) AF: 0.518 AC: 2499 AN: 4824

European-Finnish (FIN) AF: 0.479 AC: 5061 AN: 10576

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33376 AN: 67964

Other (OTH) AF: 0.445 AC: 938 AN: 2110

Alfa AF: 0.419 Hom.: 1805

Bravo AF: 0.406

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.64
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs10739410; hg19: chr9-117166034; COSMIC: COSV54328246;