5-168419639-A-G

Position:

• chr5-168419639-A-G

Variant summary

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

The ENST00000265293.9(WWC1):​c.1185-2369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,138 control chromosomes in the GnomAD database, including 15,612 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 0.43 (15612 hom., cov: 33)
• Consequence: WWC1 ENST00000265293.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC1	NM_015238.3	c.1185-2369A>G		intron_variant		ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.1185-2369A>G		intron_variant		1	NM_015238.3	ENSP00000265293	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65474 AN: 152020 Hom.: 15562 Cov.: 33

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.431 AC: 65592 AN: 152138 Hom.: 15612 Cov.: 33 AF XY: 0.435 AC XY: 32322 AN XY: 74380

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.392

Alfa AF: 0.341 Hom.: 4462

Bravo AF: 0.452

Asia WGS AF: 0.523 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.74

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: rs10462974; hg19: chr5-167846644; COSMIC: COSV54648267; COSMIC: COSV54648267;