1-68175477-A-T

Position:

• chr1-68175477-A-T

Variant summary

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

The NM_024911.7(WLS):​c.380-16230T>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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WLS	NM_024911.7	c.380-16230T>A		intron_variant		ENST00000262348.9	NP_079187.3
GNG12-AS1	NR_040077.1	n.1229-26492A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000262348.9	c.380-16230T>A		intron_variant		1	NM_024911.7	ENSP00000262348	P1
GNG12-AS1	ENST00000420587.5	n.1214-26492A>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.369

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.46

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: rs891527; hg19: chr1-68641160;