5-168419639-A-G

Variant names:

• chr5-168419639-A-G
• rs10462974
• NM_015238.3:c.1185-2369A>G

Variant summary

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

The NM_015238.3(WWC1):​c.1185-2369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,138 control chromosomes in the GnomAD database, including 15,612 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 0.43 (15612 hom., cov: 33)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015238.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWC1	NM_015238.3	MANE Select	c.1185-2369A>G		intron	N/A	NP_056053.1	Q8IX03-1
	WWC1	NM_001161661.2		c.1185-2369A>G		intron	N/A	NP_001155133.1	Q8IX03-2
	WWC1	NM_001161662.2		c.1185-2369A>G		intron	N/A	NP_001155134.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWC1	ENST00000265293.9	TSL:1 MANE Select	c.1185-2369A>G		intron	N/A	ENSP00000265293.4	Q8IX03-1
	WWC1	ENST00000393895.7	TSL:1	c.1068-2369A>G		intron	N/A	ENSP00000377473.3	H3BLZ3
	WWC1	ENST00000524228.5	TSL:1	c.513-2369A>G		intron	N/A	ENSP00000429339.1	H0YBE8

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65474 AN: 152020 Hom.: 15562 Cov.: 33

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.431 AC: 65592 AN: 152138 Hom.: 15612 Cov.: 33 AF XY: 0.435 AC XY: 32322 AN XY: 74380

African (AFR) AF: 0.585 AC: 24270 AN: 41520

American (AMR) AF: 0.494 AC: 7548 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3983 AN: 5168

South Asian (SAS) AF: 0.300 AC: 1449 AN: 4828

European-Finnish (FIN) AF: 0.419 AC: 4427 AN: 10570

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21490 AN: 67984

Other (OTH) AF: 0.392 AC: 827 AN: 2112

Alfa AF: 0.343 Hom.: 5048

Bravo AF: 0.452

Asia WGS AF: 0.523 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.74
PhyloP100		-1.4
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: rs10462974; hg19: chr5-167846644; COSMIC: COSV54648267; COSMIC: COSV54648267;