rs4576167

Positions:

• chr5-168459692-G-C

Variant summary

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

The NM_015238.3(WWC1):​c.2824-958G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,068 control chromosomes in the GnomAD database, including 8,359 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 0.31 (8359 hom., cov: 32)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC1	NM_015238.3	c.2824-958G>C		intron_variant		ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.2824-958G>C		intron_variant		1	NM_015238.3	ENSP00000265293	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46768 AN: 151950 Hom.: 8361 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.307 AC: 46760 AN: 152068 Hom.: 8359 Cov.: 32 AF XY: 0.307 AC XY: 22793 AN XY: 74336

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.0386

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.355

Alfa AF: 0.339 Hom.: 1187

Bravo AF: 0.293

Asia WGS AF: 0.251 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.85

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: rs4576167; hg19: chr5-167886697;