1-68168241-G-A

Variant names:

• chr1-68168241-G-A
• rs1367448
• NM_024911.7:c.380-8994C>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.380-8994C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,794 control chromosomes in the GnomAD database, including 10,316 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 0.36 (10316 hom., cov: 31)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 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.380-8994C>T		intron	N/A	NP_079187.3
	WLS	NM_001002292.4		c.374-8994C>T		intron	N/A	NP_001002292.3
	WLS	NM_001193334.1		c.107-8994C>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.380-8994C>T		intron	N/A	ENSP00000262348.4
	WLS	ENST00000354777.6	TSL:1	c.374-8994C>T		intron	N/A	ENSP00000346829.2
	WLS	ENST00000370976.7	TSL:1	c.107-8994C>T		intron	N/A	ENSP00000360015.3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55387 AN: 151676 Hom.: 10315 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.365 AC: 55402 AN: 151794 Hom.: 10316 Cov.: 31 AF XY: 0.368 AC XY: 27270 AN XY: 74178

African (AFR) AF: 0.358 AC: 14797 AN: 41378

American (AMR) AF: 0.456 AC: 6959 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3468

East Asian (EAS) AF: 0.507 AC: 2610 AN: 5148

South Asian (SAS) AF: 0.495 AC: 2375 AN: 4796

European-Finnish (FIN) AF: 0.334 AC: 3520 AN: 10538

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22687 AN: 67896

Other (OTH) AF: 0.390 AC: 821 AN: 2104

Alfa AF: 0.356 Hom.: 18470

Bravo AF: 0.377

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.21
PhyloP100		-0.61
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: rs1367448; hg19: chr1-68633924;