5-168418186-C-T

Variant names:

• chr5-168418186-C-T
• rs1477306
• NM_015238.3:c.1184+3596C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015238.3(WWC1):​c.1184+3596C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,996 control chromosomes in the GnomAD database, including 15,734 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 (15734 hom., cov: 32)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• 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 rank	MANE	Protein	UniProt
WWC1	NM_015238.3	c.1184+3596C>T		intron_variant	Intron 9 of 22	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.1184+3596C>T		intron_variant	Intron 9 of 22	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65778 AN: 151878 Hom.: 15684 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.434 AC: 65896 AN: 151996 Hom.: 15734 Cov.: 32 AF XY: 0.437 AC XY: 32464 AN XY: 74288

African (AFR) AF: 0.585 AC: 24257 AN: 41450

American (AMR) AF: 0.500 AC: 7645 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3962 AN: 5138

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4820

European-Finnish (FIN) AF: 0.420 AC: 4444 AN: 10574

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21601 AN: 67940

Other (OTH) AF: 0.400 AC: 841 AN: 2102

Alfa AF: 0.417 Hom.: 2136

Bravo AF: 0.455

Asia WGS AF: 0.524 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.80
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1477306; hg19: chr5-167845191; COSMIC: COSV54648199; COSMIC: COSV54648199;