1-68175477-A-T

Variant names:

• chr1-68175477-A-T
• rs891527
• NM_024911.7:c.380-16230T>A

Variant summary

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

The NM_024911.7(WLS):​c.380-16230T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,156 control chromosomes in the GnomAD database, including 10,419 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 0.37 (10419 hom., cov: 33)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 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.380-16230T>A		intron	N/A	NP_079187.3
	WLS	NM_001002292.4		c.374-16230T>A		intron	N/A	NP_001002292.3	Q5T9L3-2
	WLS	NM_001193334.1		c.107-16230T>A		intron	N/A	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.380-16230T>A		intron	N/A	ENSP00000262348.4	Q5T9L3-1
	WLS	ENST00000354777.6	TSL:1	c.374-16230T>A		intron	N/A	ENSP00000346829.2	Q5T9L3-2
	WLS	ENST00000370976.7	TSL:1	c.107-16230T>A		intron	N/A	ENSP00000360015.3	Q5T9L3-3

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55640 AN: 152038 Hom.: 10416 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.366 AC: 55673 AN: 152156 Hom.: 10419 Cov.: 33 AF XY: 0.364 AC XY: 27081 AN XY: 74380

African (AFR) AF: 0.291 AC: 12087 AN: 41506

American (AMR) AF: 0.374 AC: 5720 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1327 AN: 3472

East Asian (EAS) AF: 0.313 AC: 1617 AN: 5172

South Asian (SAS) AF: 0.391 AC: 1887 AN: 4830

European-Finnish (FIN) AF: 0.341 AC: 3610 AN: 10580

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28139 AN: 67992

Other (OTH) AF: 0.369 AC: 780 AN: 2114

Alfa AF: 0.214 Hom.: 420

Bravo AF: 0.361

Asia WGS AF: 0.391 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.46
PhyloP100		-0.47
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: rs891527; hg19: chr1-68641160;