1-68197460-C-T

Variant names:

• chr1-68197460-C-T
• rs919540
• NM_024911.7:c.107-3233G>A

Variant summary

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

The NM_024911.7(WLS):​c.107-3233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,956 control chromosomes in the GnomAD database, including 9,119 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 0.34 (9119 hom., cov: 33)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WLS	NM_024911.7	c.107-3233G>A		intron_variant	Intron 1 of 11	ENST00000262348.9	NP_079187.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000262348.9	c.107-3233G>A		intron_variant	Intron 1 of 11	1	NM_024911.7	ENSP00000262348.4

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51940 AN: 151838 Hom.: 9112 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.342 AC: 51976 AN: 151956 Hom.: 9119 Cov.: 33 AF XY: 0.338 AC XY: 25138 AN XY: 74308

African (AFR) AF: 0.399 AC: 16537 AN: 41434

American (AMR) AF: 0.315 AC: 4816 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1898 AN: 5166

South Asian (SAS) AF: 0.334 AC: 1611 AN: 4824

European-Finnish (FIN) AF: 0.202 AC: 2138 AN: 10578

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22561 AN: 67892

Other (OTH) AF: 0.353 AC: 744 AN: 2106

Alfa AF: 0.310 Hom.: 974

Bravo AF: 0.353

Asia WGS AF: 0.352 AC: 1227 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.6
DANN	Benign	0.43
PhyloP100		0.76
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: rs919540; hg19: chr1-68663143;