rs10038727

Variant names:

• chr5-168459532-G-A
• rs10038727
• NM_015238.3:c.2824-1118G>A

Variant summary

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

The NM_015238.3(WWC1):​c.2824-1118G>A 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 151,952 control chromosomes in the GnomAD database, including 8,342 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 (8342 hom., cov: 31)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3	c.2824-1118G>A		intron_variant	Intron 19 of 22	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.2824-1118G>A		intron_variant	Intron 19 of 22	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46718 AN: 151834 Hom.: 8344 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.307 AC: 46710 AN: 151952 Hom.: 8342 Cov.: 31 AF XY: 0.306 AC XY: 22749 AN XY: 74252

African (AFR) AF: 0.154 AC: 6369 AN: 41448

American (AMR) AF: 0.317 AC: 4833 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3470

East Asian (EAS) AF: 0.0388 AC: 200 AN: 5158

South Asian (SAS) AF: 0.427 AC: 2049 AN: 4802

European-Finnish (FIN) AF: 0.328 AC: 3451 AN: 10536

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26947 AN: 67964

Other (OTH) AF: 0.356 AC: 753 AN: 2114

Alfa AF: 0.378 Hom.: 20640

Bravo AF: 0.293

Asia WGS AF: 0.251 AC: 874 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	3.5
DANN	Benign	0.36
PhyloP100		-0.14
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: rs10038727; hg19: chr5-167886537;