rs2772300

Variant names:

• chr1-68182343-G-A
• rs2772300
• NM_024911.7:c.379+11612C>T

Variant summary

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

The NM_024911.7(WLS):​c.379+11612C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,134 control chromosomes in the GnomAD database, including 4,171 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 0.23 (4171 hom., cov: 33)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 9 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 (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WLS	NM_024911.7	c.379+11612C>T		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.379+11612C>T		intron_variant	Intron 2 of 11	1	NM_024911.7	ENSP00000262348.4

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34893 AN: 152016 Hom.: 4173 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.229 AC: 34900 AN: 152134 Hom.: 4171 Cov.: 33 AF XY: 0.228 AC XY: 16927 AN XY: 74374

African (AFR) AF: 0.164 AC: 6803 AN: 41526

American (AMR) AF: 0.225 AC: 3442 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1187 AN: 5152

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4822

European-Finnish (FIN) AF: 0.186 AC: 1966 AN: 10582

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18558 AN: 67984

Other (OTH) AF: 0.231 AC: 489 AN: 2114

Alfa AF: 0.261 Hom.: 22951

Bravo AF: 0.225

Asia WGS AF: 0.273 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.72
DANN	Benign	0.78
PhyloP100		-0.048
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: rs2772300; hg19: chr1-68648026;