1-68166800-C-T

Variant names:

• chr1-68166800-C-T
• rs2566758
• NM_024911.7:c.380-7553G>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.374-7553G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,988 control chromosomes in the GnomAD database, including 22,891 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 0.54 (22891 hom., cov: 32)
• Consequence: WLS NM_001002292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 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_024911.7	MANE Select	c.380-7553G>A		intron	N/A	NP_079187.3
	WLS	NM_001002292.4		c.374-7553G>A		intron	N/A	NP_001002292.3
	WLS	NM_001193334.1		c.107-7553G>A		intron	N/A	NP_001180263.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000262348.9	TSL:1 MANE Select	c.380-7553G>A		intron	N/A	ENSP00000262348.4
	WLS	ENST00000354777.6	TSL:1	c.374-7553G>A		intron	N/A	ENSP00000346829.2
	WLS	ENST00000370976.7	TSL:1	c.107-7553G>A		intron	N/A	ENSP00000360015.3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82438 AN: 151870 Hom.: 22879 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.543 AC: 82491 AN: 151988 Hom.: 22891 Cov.: 32 AF XY: 0.549 AC XY: 40781 AN XY: 74298

African (AFR) AF: 0.454 AC: 18821 AN: 41432

American (AMR) AF: 0.569 AC: 8699 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2033 AN: 3472

East Asian (EAS) AF: 0.803 AC: 4152 AN: 5172

South Asian (SAS) AF: 0.655 AC: 3157 AN: 4822

European-Finnish (FIN) AF: 0.615 AC: 6487 AN: 10552

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37323 AN: 67926

Other (OTH) AF: 0.545 AC: 1150 AN: 2110

Alfa AF: 0.547 Hom.: 17616

Bravo AF: 0.533

Asia WGS AF: 0.697 AC: 2424 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	0.72
DANN	Benign	0.84
PhyloP100		-0.67
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: rs2566758; hg19: chr1-68632483;