chr1-68170060-C-T

Position:

• chr1-68170060-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024911.7(WLS):​c.380-10813G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,934 control chromosomes in the GnomAD database, including 9,599 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 0.35 (9599 hom., cov: 32)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WLS	NM_024911.7	c.380-10813G>A		intron_variant		ENST00000262348.9	NP_079187.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000262348.9	c.380-10813G>A		intron_variant		1	NM_024911.7	ENSP00000262348.4

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52513 AN: 151820 Hom.: 9595 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.346 AC: 52540 AN: 151934 Hom.: 9599 Cov.: 32 AF XY: 0.347 AC XY: 25743 AN XY: 74230

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.346

Alfa AF: 0.299 Hom.: 1143

Bravo AF: 0.333

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs2195682; hg19: chr1-68635743; COSMIC: COSV52038784;