chr1-68155079-G-A

Position:

• chr1-68155079-G-A

Variant summary

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

The NM_024911.7(WLS):​c.666+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,609,386 control chromosomes in the GnomAD database, including 128,561 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 0.34 (9445 hom., cov: 32)
  • Exomes 𝑓: 0.40 (119116 hom.)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WLS	NM_024911.7	c.666+20C>T		intron_variant		ENST00000262348.9	NP_079187.3
GNG12-AS1	NR_040077.1	n.1228+16629G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000262348.9	c.666+20C>T		intron_variant		1	NM_024911.7	ENSP00000262348	P1
GNG12-AS1	ENST00000420587.5	n.1213+16629G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51150 AN: 151896 Hom.: 9444 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.372

GnomAD3 exomes AF: 0.364 AC: 90171 AN: 247780 Hom.: 17644 AF XY: 0.366 AC XY: 48981 AN XY: 133904

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.442

Gnomad EAS exome AF: 0.159

Gnomad SAS exome AF: 0.319

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.398 AC: 579982 AN: 1457374 Hom.: 119116 Cov.: 33 AF XY: 0.397 AC XY: 287845 AN XY: 724726

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.441

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.337 AC: 51170 AN: 152012 Hom.: 9445 Cov.: 32 AF XY: 0.332 AC XY: 24699 AN XY: 74304

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.375

Alfa AF: 0.408 Hom.: 18249

Bravo AF: 0.338

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
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: rs3762371; hg19: chr1-68620762; COSMIC: COSV52041593; COSMIC: COSV52041593;