9-114404267-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015404.4(WHRN):c.2237-190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,946 control chromosomes in the GnomAD database, including 3,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3577 hom., cov: 32)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.886

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-114404267-A-G is Benign according to our data. Variant chr9-114404267-A-G is described in ClinVar as [Benign]. Clinvar id is 678811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WHRN	NM_015404.4	c.2237-190T>C		intron_variant		ENST00000362057.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WHRN	ENST00000362057.4	c.2237-190T>C		intron_variant		1	NM_015404.4	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30487 AN: 151824 Hom.: 3571 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.201 AC: 30508 AN: 151946 Hom.: 3577 Cov.: 32 AF XY: 0.205 AC XY: 15189 AN XY: 74252

Gnomad4 AFR AF: 0.0757

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.217

Alfa AF: 0.108 Hom.: 169

Bravo AF: 0.196

Asia WGS AF: 0.245 AC: 849 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.89
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs766835; hg19: chr9-117166547;