rs55833018

chr9-114403457-C-T

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.2419-118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,391,338 control chromosomes in the GnomAD database, including 45,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3672 hom., cov: 33)
  • Exomes 𝑓: 0.25 (41665 hom.)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.59

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 9-114403457-C-T is Benign according to our data. Variant chr9-114403457-C-T is described in ClinVar as [Benign]. Clinvar id is 1243163.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-114403457-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WHRN	NM_015404.4	c.2419-118G>A		intron_variant		ENST00000362057.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WHRN	ENST00000362057.4	c.2419-118G>A		intron_variant		1	NM_015404.4	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32269 AN: 152056 Hom.: 3673 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.254 AC: 315115 AN: 1239164 Hom.: 41665 AF XY: 0.257 AC XY: 160624 AN XY: 625840

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.212 AC: 32272 AN: 152174 Hom.: 3672 Cov.: 33 AF XY: 0.208 AC XY: 15457 AN XY: 74400

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.226

Alfa AF: 0.235 Hom.: 550

Bravo AF: 0.208

Asia WGS AF: 0.168 AC: 585 AN: 3478

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

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.027
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs55833018; hg19: chr9-117165737;