5-168431457-TCTGGCTGGCTGGCTGGCTGGCTGGCTGGCTGG-TCTGGCTGGCTGGCTGGCTGGCTGG

Variant names:

• chr5-168431457-TCTGGCTGG-T
• rs11279828
• NM_015238.3:c.2280+53_2280+60delGCTGGCTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015238.3(WWC1):​c.2280+53_2280+60delGCTGGCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,391,104 control chromosomes in the GnomAD database, including 162,812 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (21480 hom., cov: 0)
  • Exomes 𝑓: 0.48 (141332 hom.)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3	c.2280+53_2280+60delGCTGGCTG		intron_variant	Intron 15 of 22	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.2280+14_2280+21delCTGGCTGG		intron_variant	Intron 15 of 22	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.534 AC: 79032 AN: 148112 Hom.: 21457 Cov.: 0

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.503

GnomAD2 exomes AF: 0.535 AC: 67723 AN: 126504 AF XY: 0.533

Gnomad AFR exome AF: 0.549

Gnomad AMR exome AF: 0.633

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.716

Gnomad FIN exome AF: 0.479

Gnomad NFE exome AF: 0.470

Gnomad OTH exome AF: 0.499

GnomAD4 exome AF: 0.479 AC: 595789 AN: 1242884 Hom.: 141332 AF XY: 0.480 AC XY: 295899 AN XY: 616098

African (AFR) AF: 0.552 AC: 15737 AN: 28506

American (AMR) AF: 0.592 AC: 18844 AN: 31830

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 9583 AN: 20118

East Asian (EAS) AF: 0.653 AC: 23432 AN: 35872

South Asian (SAS) AF: 0.518 AC: 35233 AN: 68004

European-Finnish (FIN) AF: 0.464 AC: 16148 AN: 34796

Middle Eastern (MID) AF: 0.408 AC: 1877 AN: 4606

European-Non Finnish (NFE) AF: 0.465 AC: 449430 AN: 966826

Other (OTH) AF: 0.487 AC: 25505 AN: 52326

GnomAD4 genome AF: 0.534 AC: 79091 AN: 148220 Hom.: 21480 Cov.: 0 AF XY: 0.538 AC XY: 38787 AN XY: 72060

African (AFR) AF: 0.604 AC: 24303 AN: 40212

American (AMR) AF: 0.560 AC: 8327 AN: 14860

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1757 AN: 3428

East Asian (EAS) AF: 0.734 AC: 3643 AN: 4962

South Asian (SAS) AF: 0.551 AC: 2431 AN: 4410

European-Finnish (FIN) AF: 0.472 AC: 4782 AN: 10128

Middle Eastern (MID) AF: 0.421 AC: 122 AN: 290

European-Non Finnish (NFE) AF: 0.480 AC: 32157 AN: 67010

Other (OTH) AF: 0.503 AC: 1017 AN: 2020

Alfa AF: 0.445 Hom.: 1588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11279828; hg19: chr5-167858462;