chr1-68159195-C-T

Variant names:

• chr1-68159195-C-T
• rs3748705
• NM_024911.7:c.432G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_024911.7(WLS):​c.432G>A​(p.Ala144Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,613,290 control chromosomes in the GnomAD database, including 99,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8895 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90392 hom.)
• Consequence: WLS NM_024911.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650
• Publications: 28 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.018).
• BP6: Variant 1-68159195-C-T is Benign according to our data. Variant chr1-68159195-C-T is described in ClinVar as Benign. ClinVar VariationId is 2585666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.065 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024911.7. 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_024911.7	MANE Select	c.432G>A	p.Ala144Ala	synonymous	Exon 3 of 12	NP_079187.3
	WLS	NM_001002292.4		c.426G>A	p.Ala142Ala	synonymous	Exon 3 of 12	NP_001002292.3	Q5T9L3-2
	WLS	NM_001193334.1		c.159G>A	p.Ala53Ala	synonymous	Exon 2 of 11	NP_001180263.1	Q5T9L3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000262348.9	TSL:1 MANE Select	c.432G>A	p.Ala144Ala	synonymous	Exon 3 of 12	ENSP00000262348.4	Q5T9L3-1
	WLS	ENST00000354777.6	TSL:1	c.426G>A	p.Ala142Ala	synonymous	Exon 3 of 12	ENSP00000346829.2	Q5T9L3-2
	WLS	ENST00000370976.7	TSL:1	c.159G>A	p.Ala53Ala	synonymous	Exon 2 of 11	ENSP00000360015.3	Q5T9L3-3

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50657 AN: 151832 Hom.: 8894 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.343

GnomAD2 exomes AF: 0.367 AC: 92178 AN: 251192 AF XY: 0.367

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.456

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.352

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.349 AC: 510128 AN: 1461338 Hom.: 90392 Cov.: 38 AF XY: 0.349 AC XY: 253482 AN XY: 726966

African (AFR) AF: 0.245 AC: 8199 AN: 33460

American (AMR) AF: 0.400 AC: 17870 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7532 AN: 26110

East Asian (EAS) AF: 0.433 AC: 17185 AN: 39676

South Asian (SAS) AF: 0.353 AC: 30416 AN: 86164

European-Finnish (FIN) AF: 0.458 AC: 24467 AN: 53394

Middle Eastern (MID) AF: 0.364 AC: 2100 AN: 5764

European-Non Finnish (NFE) AF: 0.343 AC: 381251 AN: 1111734

Other (OTH) AF: 0.350 AC: 21108 AN: 60372

GnomAD4 genome AF: 0.334 AC: 50680 AN: 151952 Hom.: 8895 Cov.: 32 AF XY: 0.339 AC XY: 25174 AN XY: 74250

African (AFR) AF: 0.246 AC: 10206 AN: 41460

American (AMR) AF: 0.383 AC: 5842 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2245 AN: 5148

South Asian (SAS) AF: 0.365 AC: 1760 AN: 4818

European-Finnish (FIN) AF: 0.458 AC: 4824 AN: 10544

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23609 AN: 67944

Other (OTH) AF: 0.342 AC: 721 AN: 2106

Alfa AF: 0.341 Hom.: 15311

Bravo AF: 0.326

Asia WGS AF: 0.373 AC: 1296 AN: 3478

EpiCase AF: 0.351

EpiControl AF: 0.346

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Zaki syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.0
DANN	Benign	0.75
PhyloP100		0.065
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: rs3748705; hg19: chr1-68624878; COSMIC: COSV52041744; COSMIC: COSV52041744;