rs3736934

Positions:

• chr1-68122454-C-T

Variant summary

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

The ENST00000354777.6(WLS):​c.1510+15326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,068 control chromosomes in the GnomAD database, including 7,644 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 0.32 (7644 hom., cov: 33)
• Consequence: WLS ENST00000354777.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330

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 (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG12-AS1	NR_040077.1	n.1074+1213C>T		intron_variant, non_coding_transcript_variant
WLS	NM_001002292.4	c.1510+15326G>A		intron_variant			NP_001002292.3
WLS	XM_011542191.3	c.1516+15326G>A		intron_variant			XP_011540493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000354777.6	c.1510+15326G>A		intron_variant		1		ENSP00000346829
GNG12-AS1	ENST00000420587.5	n.1059+1213C>T		intron_variant, non_coding_transcript_variant		2
GNG12-AS1	ENST00000413628.5	n.1039+1213C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48062 AN: 151950 Hom.: 7639 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.316 AC: 48097 AN: 152068 Hom.: 7644 Cov.: 33 AF XY: 0.318 AC XY: 23626 AN XY: 74334

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.323

Alfa AF: 0.305 Hom.: 3688

Bravo AF: 0.317

Asia WGS AF: 0.408 AC: 1419 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	0.93
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3736934; hg19: chr1-68588137;