rs187922

Positions:

• chr1-68111137-A-G
• chr1-68111137-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354777.6(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 ENST00000354777.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG12-AS1	NR_040077.1	n.676-6314A>G		intron_variant, non_coding_transcript_variant
WLS	NM_001002292.4	c.1511-12384T>C		intron_variant			NP_001002292.3
WLS	XM_011542191.3	c.1517-12384T>C		intron_variant			XP_011540493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000354777.6	c.1511-12384T>C		intron_variant		1		ENSP00000346829
GNG12-AS1	ENST00000420587.5	n.661-6314A>G		intron_variant, non_coding_transcript_variant		2
GNG12-AS1	ENST00000413628.5	n.641-6314A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.984

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.938

Alfa AF: 0.943 Hom.: 74615

Bravo AF: 0.941

Asia WGS AF: 0.762 AC: 2650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs187922; hg19: chr1-68576820;