rs1422422

chr5-168305795-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015238.3(WWC1):c.119+13524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,934 control chromosomes in the GnomAD database, including 32,074 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 0.65 (32074 hom., cov: 31)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

Genes affected

WWC1 (HGNC:29435): (WW and C2 domain containing 1) The protein encoded by this gene is a cytoplasmic phosphoprotein that interacts with PRKC-zeta and dynein light chain-1. Alleles of this gene have been found that enhance memory in some individuals. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC1	NM_015238.3	c.119+13524T>C		intron_variant		ENST00000265293.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC1	ENST00000265293.9	c.119+13524T>C		intron_variant		1	NM_015238.3	P1
WWC1	ENST00000521089.5	c.119+13524T>C		intron_variant		2
WWC1	ENST00000523043.5	n.26+13524T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98279 AN: 151816 Hom.: 32059 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.647 AC: 98333 AN: 151934 Hom.: 32074 Cov.: 31 AF XY: 0.646 AC XY: 47971 AN XY: 74274

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.663

Alfa AF: 0.669 Hom.: 15688

Bravo AF: 0.647

Asia WGS AF: 0.598 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.7
Dann	Benign	0.82

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: rs1422422; hg19: chr5-167732800; COSMIC: COSV54646256;