XM_017009826.2:c.-220-2070G>A

Variant names:

• chr5-138082180-G-A
• rs4835761
• XM_017009826.2:c.-220-2070G>A

Variant summary

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

The XM_017009826.2(WNT8A):​c.-220-2070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,054 control chromosomes in the GnomAD database, including 15,207 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 0.44 (15207 hom., cov: 32)
• Consequence: WNT8A XM_017009826.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 4 publications found

Genes affected

WNT8A (HGNC:12788): (Wnt family member 8A) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family, and may be implicated in development of early embryos as well as germ cell tumors. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2014]

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 = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT8A	XM_017009826.2	c.-220-2070G>A		intron_variant	Intron 2 of 6		XP_016865315.1
WNT8A	XM_047417692.1	c.-220-2070G>A		intron_variant	Intron 3 of 7		XP_047273648.1
WNT8A	XM_047417693.1	c.-220-2070G>A		intron_variant	Intron 1 of 5		XP_047273649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66587 AN: 151936 Hom.: 15206 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.438 AC: 66614 AN: 152054 Hom.: 15207 Cov.: 32 AF XY: 0.442 AC XY: 32837 AN XY: 74308

African (AFR) AF: 0.328 AC: 13604 AN: 41472

American (AMR) AF: 0.457 AC: 6971 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1864 AN: 3472

East Asian (EAS) AF: 0.606 AC: 3124 AN: 5158

South Asian (SAS) AF: 0.506 AC: 2441 AN: 4828

European-Finnish (FIN) AF: 0.468 AC: 4953 AN: 10578

Middle Eastern (MID) AF: 0.569 AC: 165 AN: 290

European-Non Finnish (NFE) AF: 0.471 AC: 32026 AN: 67978

Other (OTH) AF: 0.472 AC: 996 AN: 2108

Alfa AF: 0.466 Hom.: 5255

Bravo AF: 0.432

Asia WGS AF: 0.560 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.21
PhyloP100		-0.019

Splicing

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

Other links and lift over

dbSNP: rs4835761; hg19: chr5-137417869; COSMIC: COSV64230945;