rs12514426

Variant names:

• chr5-168466703-G-A
• rs12514426
• NM_015238.3:c.3151-1137G>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.3151-1137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,182 control chromosomes in the GnomAD database, including 1,928 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 0.12 (1928 hom., cov: 32)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3	c.3151-1137G>A		intron_variant	Intron 21 of 22	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.3151-1137G>A		intron_variant	Intron 21 of 22	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18212 AN: 152064 Hom.: 1923 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.120 AC: 18239 AN: 152182 Hom.: 1928 Cov.: 32 AF XY: 0.123 AC XY: 9124 AN XY: 74404

African (AFR) AF: 0.239 AC: 9931 AN: 41486

American (AMR) AF: 0.212 AC: 3245 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1403 AN: 5182

South Asian (SAS) AF: 0.122 AC: 589 AN: 4820

European-Finnish (FIN) AF: 0.0316 AC: 335 AN: 10606

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0321 AC: 2185 AN: 68008

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.0765 Hom.: 126

Bravo AF: 0.141

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.69
PhyloP100		-0.32
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: rs12514426; hg19: chr5-167893708;