chr5-168431457-TCTGG-T

Variant names:

• chr5-168431457-TCTGG-T
• rs11279828
• NM_015238.3:c.2280+57_2280+60delGCTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015238.3(WWC1):​c.2280+57_2280+60delGCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,406,984 control chromosomes in the GnomAD database, including 105,519 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11745 hom., cov: 0)
  • Exomes 𝑓: 0.39 (93774 hom.)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527
• 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 -10 ACMG points.

• BP6: Variant 5-168431457-TCTGG-T is Benign according to our data. Variant chr5-168431457-TCTGG-T is described in ClinVar as Benign. ClinVar VariationId is 403611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3	c.2280+57_2280+60delGCTG		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+17delCTGG		intron_variant	Intron 15 of 22	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 56792 AN: 148060 Hom.: 11741 Cov.: 0

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.428

GnomAD2 exomes AF: 0.349 AC: 44091 AN: 126504 AF XY: 0.357

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.186

Gnomad FIN exome AF: 0.376

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.388 AC: 488354 AN: 1258818 Hom.: 93774 AF XY: 0.390 AC XY: 243934 AN XY: 624868

African (AFR) AF: 0.223 AC: 6381 AN: 28604

American (AMR) AF: 0.310 AC: 9930 AN: 32078

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 8056 AN: 20442

East Asian (EAS) AF: 0.221 AC: 7970 AN: 36020

South Asian (SAS) AF: 0.379 AC: 26259 AN: 69252

European-Finnish (FIN) AF: 0.411 AC: 14588 AN: 35524

Middle Eastern (MID) AF: 0.461 AC: 2151 AN: 4666

European-Non Finnish (NFE) AF: 0.401 AC: 392411 AN: 979188

Other (OTH) AF: 0.389 AC: 20608 AN: 53044

GnomAD4 genome AF: 0.383 AC: 56818 AN: 148166 Hom.: 11745 Cov.: 0 AF XY: 0.381 AC XY: 27476 AN XY: 72038

African (AFR) AF: 0.244 AC: 9802 AN: 40208

American (AMR) AF: 0.391 AC: 5796 AN: 14840

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1452 AN: 3426

East Asian (EAS) AF: 0.192 AC: 952 AN: 4958

South Asian (SAS) AF: 0.403 AC: 1775 AN: 4402

European-Finnish (FIN) AF: 0.467 AC: 4735 AN: 10134

Middle Eastern (MID) AF: 0.483 AC: 140 AN: 290

European-Non Finnish (NFE) AF: 0.463 AC: 30989 AN: 66986

Other (OTH) AF: 0.429 AC: 867 AN: 2020

Alfa AF: 0.434 Hom.: 1588

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53
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: rs11279828; hg19: chr5-167858462;