rs1367448

Positions:

• chr1-68168241-G-A
• chr1-68168241-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WLS	NM_024911.7	c.380-8994C>T		intron_variant		ENST00000262348.9	NP_079187.3
GNG12-AS1	NR_040077.1	n.1228+29791G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000262348.9	c.380-8994C>T		intron_variant		1	NM_024911.7	ENSP00000262348	P1
GNG12-AS1	ENST00000420587.5	n.1213+29791G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.390

Alfa AF: 0.352 Hom.: 12970

Bravo AF: 0.377

Asia WGS AF: 0.458 AC: 1592 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	0.55
DANN	Benign	0.21

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: rs1367448; hg19: chr1-68633924;