1-68116774-G-T

Variant names:

• chr1-68116774-G-T
• rs2566762
• ENST00000354777.6:c.1511-18021C>A

Variant summary

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

The NM_001002292.4(WLS):​c.1511-18021C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 152,236 control chromosomes in the GnomAD database, including 249 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 0.053 (249 hom., cov: 33)
• Consequence: WLS NM_001002292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803
• Publications: 4 publications found

Genes affected

WLS (HGNC:30238): (Wnt ligand secretion mediator) Enables Wnt-protein binding activity and identical protein binding activity. Involved in positive regulation of cell communication and protein transport. Located in several cellular components, including Golgi apparatus; early endosome; and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

GNG12-AS1 (HGNC:43938): (GNG12, DIRAS3 and WLS antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002292.4. 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
	WLS	NM_001002292.4		c.1511-18021C>A		intron	N/A	NP_001002292.3	Q5T9L3-2
	GNG12-AS1	NR_040077.1		n.676-677G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000354777.6	TSL:1	c.1511-18021C>A		intron	N/A	ENSP00000346829.2	Q5T9L3-2
	GNG12-AS1	ENST00000413628.5	TSL:2	n.641-677G>T		intron	N/A
	GNG12-AS1	ENST00000420587.5	TSL:2	n.661-677G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 8004 AN: 152118 Hom.: 245 Cov.: 33

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0527 AC: 8020 AN: 152236 Hom.: 249 Cov.: 33 AF XY: 0.0507 AC XY: 3775 AN XY: 74444

African (AFR) AF: 0.0918 AC: 3810 AN: 41522

American (AMR) AF: 0.0412 AC: 630 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3470

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5176

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4826

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10626

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0418 AC: 2843 AN: 68008

Other (OTH) AF: 0.0531 AC: 112 AN: 2110

Alfa AF: 0.0465 Hom.: 544

Bravo AF: 0.0567

Asia WGS AF: 0.0230 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.34
DANN	Benign	0.36
PhyloP100		-0.80
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: rs2566762; hg19: chr1-68582457;