rs3736934

Variant names:

• chr1-68122454-C-T
• rs3736934
• ENST00000354777.6:c.1510+15326G>A

Variant summary

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

The NM_001002292.4(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 NM_001002292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.436 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.1510+15326G>A		intron	N/A	NP_001002292.3	Q5T9L3-2
	GNG12-AS1	NR_040077.1		n.1074+1213C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000354777.6	TSL:1	c.1510+15326G>A		intron	N/A	ENSP00000346829.2	Q5T9L3-2
	GNG12-AS1	ENST00000786419.1		n.1541C>T		non_coding_transcript_exon	Exon 5 of 5
	GNG12-AS1	ENST00000413628.5	TSL:2	n.1039+1213C>T		intron	N/A

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

African (AFR) AF: 0.319 AC: 13219 AN: 41450

American (AMR) AF: 0.326 AC: 4989 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3466

East Asian (EAS) AF: 0.452 AC: 2338 AN: 5176

South Asian (SAS) AF: 0.324 AC: 1560 AN: 4812

European-Finnish (FIN) AF: 0.311 AC: 3288 AN: 10584

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20606 AN: 67978

Other (OTH) AF: 0.323 AC: 682 AN: 2114

Alfa AF: 0.304 Hom.: 4036

Bravo AF: 0.317

Asia WGS AF: 0.408 AC: 1419 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	0.93
DANN	Benign	0.50
PhyloP100		-0.33
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: rs3736934; hg19: chr1-68588137;