rs1367447

Variant names:

• chr1-68168347-C-T
• rs1367447
• NM_024911.7:c.380-9100G>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.380-9100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,148 control chromosomes in the GnomAD database, including 2,410 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 0.17 (2410 hom., cov: 32)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 12 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WLS	NM_024911.7	c.380-9100G>A		intron_variant	Intron 2 of 11	ENST00000262348.9	NP_079187.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000262348.9	c.380-9100G>A		intron_variant	Intron 2 of 11	1	NM_024911.7	ENSP00000262348.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25797 AN: 152030 Hom.: 2407 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.170 AC: 25813 AN: 152148 Hom.: 2410 Cov.: 32 AF XY: 0.170 AC XY: 12623 AN XY: 74394

African (AFR) AF: 0.108 AC: 4468 AN: 41526

American (AMR) AF: 0.169 AC: 2578 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1245 AN: 5156

South Asian (SAS) AF: 0.212 AC: 1022 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1648 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13580 AN: 67974

Other (OTH) AF: 0.164 AC: 346 AN: 2112

Alfa AF: 0.190 Hom.: 4926

Bravo AF: 0.165

Asia WGS AF: 0.228 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.24
PhyloP100		-0.53
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: rs1367447; hg19: chr1-68634030;