rs1430740

chr1-68191827-T-C

Variant summary

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

The NM_024911.7(WLS):c.379+2128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,910 control chromosomes in the GnomAD database, including 26,102 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 0.58 (26102 hom., cov: 31)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WLS	NM_024911.7	c.379+2128A>G		intron_variant		ENST00000262348.9
GNG12-AS1	NR_040077.1	n.1229-10142T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WLS	ENST00000262348.9	c.379+2128A>G		intron_variant		1	NM_024911.7	P1
GNG12-AS1	ENST00000420587.5	n.1214-10142T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88403 AN: 151790 Hom.: 26082 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.582 AC: 88466 AN: 151910 Hom.: 26102 Cov.: 31 AF XY: 0.584 AC XY: 43349 AN XY: 74246

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.560

Alfa AF: 0.613 Hom.: 6606

Bravo AF: 0.567

Asia WGS AF: 0.545 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.38
Dann	Benign	0.51

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: rs1430740; hg19: chr1-68657510;