1-68111137-A-G

Variant names:

• chr1-68111137-A-G
• rs187922
• ENST00000354777.6:c.1511-12384T>C

Variant summary

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

The NM_001002292.4(WLS):​c.1511-12384T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,310 control chromosomes in the GnomAD database, including 67,756 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 0.94 (67756 hom., cov: 32)
• Consequence: WLS NM_001002292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 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_001002292.4		c.1511-12384T>C		intron	N/A	NP_001002292.3	Q5T9L3-2
	GNG12-AS1	NR_040077.1		n.676-6314A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000354777.6	TSL:1	c.1511-12384T>C		intron	N/A	ENSP00000346829.2	Q5T9L3-2
	GNG12-AS1	ENST00000413628.5	TSL:2	n.641-6314A>G		intron	N/A
	GNG12-AS1	ENST00000420587.5	TSL:2	n.661-6314A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143174 AN: 152192 Hom.: 67697 Cov.: 32

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.938

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

GnomAD4 genome AF: 0.941 AC: 143291 AN: 152310 Hom.: 67756 Cov.: 32 AF XY: 0.937 AC XY: 69774 AN XY: 74472

African (AFR) AF: 0.984 AC: 40921 AN: 41574

American (AMR) AF: 0.917 AC: 14021 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3258 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3307 AN: 5168

South Asian (SAS) AF: 0.832 AC: 4013 AN: 4824

European-Finnish (FIN) AF: 0.955 AC: 10140 AN: 10622

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64510 AN: 68038

Other (OTH) AF: 0.938 AC: 1980 AN: 2112

Alfa AF: 0.944 Hom.: 93471

Bravo AF: 0.941

Asia WGS AF: 0.762 AC: 2650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.36
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs187922; hg19: chr1-68576820;