1-68116774-G-T

Position:

• chr1-68116774-G-T

Variant summary

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

The NM_001002292.4(WLS):​c.1511-18021C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 152,236 control chromosomes in the GnomAD database, including 249 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 0.053 (249 hom., cov: 33)
• Consequence: WLS NM_001002292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WLS	NM_001002292.4	c.1511-18021C>A		intron_variant			NP_001002292.3
WLS	XM_011542191.3	c.1517-18021C>A		intron_variant			XP_011540493.1
GNG12-AS1	NR_040077.1	n.676-677G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000354777.6	c.1511-18021C>A		intron_variant		1		ENSP00000346829.2
GNG12-AS1	ENST00000413628.5	n.641-677G>T		intron_variant		2
GNG12-AS1	ENST00000420587.5	n.661-677G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 8004 AN: 152118 Hom.: 245 Cov.: 33

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0527 AC: 8020 AN: 152236 Hom.: 249 Cov.: 33 AF XY: 0.0507 AC XY: 3775 AN XY: 74444

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.0412

Gnomad4 ASJ AF: 0.0614

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0436 Hom.: 221

Bravo AF: 0.0567

Asia WGS AF: 0.0230 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.34
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2566762; hg19: chr1-68582457;