NM_024911.7:c.380-10145A>G

Variant names:

• chr1-68169392-T-C
• rs1430742
• NM_024911.7:c.380-10145A>G

Variant summary

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

The NM_024911.7(WLS):​c.380-10145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,090 control chromosomes in the GnomAD database, including 2,813 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 0.19 (2813 hom., cov: 32)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 31 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 (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024911.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	NM_024911.7	MANE Select	c.380-10145A>G		intron	N/A	NP_079187.3
	WLS	NM_001002292.4		c.374-10145A>G		intron	N/A	NP_001002292.3
	WLS	NM_001193334.1		c.107-10145A>G		intron	N/A	NP_001180263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000262348.9	TSL:1 MANE Select	c.380-10145A>G		intron	N/A	ENSP00000262348.4
	WLS	ENST00000354777.6	TSL:1	c.374-10145A>G		intron	N/A	ENSP00000346829.2
	WLS	ENST00000370976.7	TSL:1	c.107-10145A>G		intron	N/A	ENSP00000360015.3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28468 AN: 151972 Hom.: 2812 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.187 AC: 28475 AN: 152090 Hom.: 2813 Cov.: 32 AF XY: 0.188 AC XY: 13989 AN XY: 74362

African (AFR) AF: 0.132 AC: 5462 AN: 41492

American (AMR) AF: 0.188 AC: 2871 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1204 AN: 5152

South Asian (SAS) AF: 0.254 AC: 1225 AN: 4828

European-Finnish (FIN) AF: 0.157 AC: 1659 AN: 10596

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14681 AN: 67948

Other (OTH) AF: 0.189 AC: 399 AN: 2110

Alfa AF: 0.207 Hom.: 10160

Bravo AF: 0.183

Asia WGS AF: 0.266 AC: 931 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	0.016
DANN	Benign	0.52
PhyloP100		-2.3
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: rs1430742; hg19: chr1-68635075;