rs1535971

Variant names:

• chr9-114467120-T-A
• rs1535971
• NM_015404.4:c.838-728A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-114467120-T-A
• chr9-114467120-T-C
• chr9-114467120-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_015404.4(WHRN):​c.838-728A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 150,058 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0012 (0 hom., cov: 28)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00115 (173/150058) while in subpopulation NFE AF = 0.0019 (128/67460). AF 95% confidence interval is 0.00163. There are 0 homozygotes in GnomAd4. There are 75 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WHRN	NM_015404.4	c.838-728A>T		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.838-728A>T		intron_variant	Intron 2 of 11	1	NM_015404.4	ENSP00000354623.3

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 173 AN: 149934 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000330

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00188

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00980

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00291

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

GnomAD4 genome AF: 0.00115 AC: 173 AN: 150058 Hom.: 0 Cov.: 28 AF XY: 0.00102 AC XY: 75 AN XY: 73320

African (AFR) AF: 0.000520 AC: 21 AN: 40408

American (AMR) AF: 0.000329 AC: 5 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.00189 AC: 9 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10434

Middle Eastern (MID) AF: 0.0106 AC: 3 AN: 284

European-Non Finnish (NFE) AF: 0.00190 AC: 128 AN: 67460

Other (OTH) AF: 0.00288 AC: 6 AN: 2084

Alfa AF: 0.00000746 Hom.: 69563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.35
PhyloP100		-2.7

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: rs1535971; hg19: chr9-117229400;