chr1-68155079-G-A

Variant names:

• chr1-68155079-G-A
• rs3762371
• NM_024911.7:c.666+20C>T

Variant summary

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

The NM_024911.7(WLS):​c.666+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,609,386 control chromosomes in the GnomAD database, including 128,561 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 0.34 (9445 hom., cov: 32)
  • Exomes 𝑓: 0.40 (119116 hom.)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	NM_024911.7	MANE Select	c.666+20C>T		intron	N/A	NP_079187.3
	WLS	NM_001002292.4		c.660+20C>T		intron	N/A	NP_001002292.3
	WLS	NM_001193334.1		c.393+20C>T		intron	N/A	NP_001180263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000262348.9	TSL:1 MANE Select	c.666+20C>T		intron	N/A	ENSP00000262348.4
	WLS	ENST00000354777.6	TSL:1	c.660+20C>T		intron	N/A	ENSP00000346829.2
	WLS	ENST00000370976.7	TSL:1	c.393+20C>T		intron	N/A	ENSP00000360015.3

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51150 AN: 151896 Hom.: 9444 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.372

GnomAD2 exomes AF: 0.364 AC: 90171 AN: 247780 AF XY: 0.366

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.442

Gnomad EAS exome AF: 0.159

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.398 AC: 579982 AN: 1457374 Hom.: 119116 Cov.: 33 AF XY: 0.397 AC XY: 287845 AN XY: 724726

African (AFR) AF: 0.186 AC: 6220 AN: 33402

American (AMR) AF: 0.426 AC: 18905 AN: 44406

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 11401 AN: 25868

East Asian (EAS) AF: 0.150 AC: 5939 AN: 39600

South Asian (SAS) AF: 0.325 AC: 27800 AN: 85506

European-Finnish (FIN) AF: 0.311 AC: 16500 AN: 52990

Middle Eastern (MID) AF: 0.357 AC: 2053 AN: 5754

European-Non Finnish (NFE) AF: 0.422 AC: 468410 AN: 1109636

Other (OTH) AF: 0.378 AC: 22754 AN: 60212

GnomAD4 genome AF: 0.337 AC: 51170 AN: 152012 Hom.: 9445 Cov.: 32 AF XY: 0.332 AC XY: 24699 AN XY: 74304

African (AFR) AF: 0.201 AC: 8344 AN: 41486

American (AMR) AF: 0.396 AC: 6052 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1540 AN: 3462

East Asian (EAS) AF: 0.160 AC: 825 AN: 5162

South Asian (SAS) AF: 0.308 AC: 1484 AN: 4818

European-Finnish (FIN) AF: 0.307 AC: 3243 AN: 10564

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28446 AN: 67942

Other (OTH) AF: 0.375 AC: 790 AN: 2104

Alfa AF: 0.402 Hom.: 22369

Bravo AF: 0.338

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.88
Mutation Taster		=99/1	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: rs3762371; hg19: chr1-68620762; COSMIC: COSV52041593; COSMIC: COSV52041593;