5-168317202-T-C

Variant names:

• chr5-168317202-T-C
• rs4976592
• NM_015238.3:c.119+24931T>C

Variant summary

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

The NM_015238.3(WWC1):​c.119+24931T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,102 control chromosomes in the GnomAD database, including 38,998 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 0.71 (38998 hom., cov: 32)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 4 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]

ENSG00000296875 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3	c.119+24931T>C		intron_variant	Intron 1 of 22	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.119+24931T>C		intron_variant	Intron 1 of 22	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108601 AN: 151986 Hom.: 38977 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.714 AC: 108665 AN: 152102 Hom.: 38998 Cov.: 32 AF XY: 0.712 AC XY: 52964 AN XY: 74366

African (AFR) AF: 0.685 AC: 28423 AN: 41476

American (AMR) AF: 0.717 AC: 10964 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2639 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3025 AN: 5174

South Asian (SAS) AF: 0.701 AC: 3378 AN: 4816

European-Finnish (FIN) AF: 0.727 AC: 7694 AN: 10580

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50069 AN: 67978

Other (OTH) AF: 0.723 AC: 1527 AN: 2112

Alfa AF: 0.729 Hom.: 20464

Bravo AF: 0.713

Asia WGS AF: 0.615 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.36
PhyloP100		-1.3
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: rs4976592; hg19: chr5-167744207;