rs2790457

chr10-28567890-G-Achr10-28567890-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016628.5(WAC):c.275-15509G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,884 control chromosomes in the GnomAD database, including 10,050 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 0.35 (10050 hom., cov: 31)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

WAC (HGNC:17327): (WW domain containing adaptor with coiled-coil) The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WAC	NM_016628.5	c.275-15509G>A		intron_variant		ENST00000354911.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WAC	ENST00000354911.9	c.275-15509G>A		intron_variant		1	NM_016628.5	P3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53168 AN: 151766 Hom.: 10044 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.350 AC: 53189 AN: 151884 Hom.: 10050 Cov.: 31 AF XY: 0.354 AC XY: 26252 AN XY: 74210

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.367

Alfa AF: 0.315 Hom.: 1260

Bravo AF: 0.367

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.6
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs2790457; hg19: chr10-28856819;