chr1-68182033-T-C

Variant names:

• chr1-68182033-T-C
• rs12407028
• NM_024911.7:c.379+11922A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024911.7(WLS):​c.379+11922A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,006 control chromosomes in the GnomAD database, including 9,582 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 0.35 (9582 hom., cov: 32)
• Consequence: WLS NM_024911.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WLS	NM_024911.7	c.379+11922A>G		intron_variant	Intron 2 of 11	ENST00000262348.9	NP_079187.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000262348.9	c.379+11922A>G		intron_variant	Intron 2 of 11	1	NM_024911.7	ENSP00000262348.4

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52603 AN: 151888 Hom.: 9577 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.346 AC: 52637 AN: 152006 Hom.: 9582 Cov.: 32 AF XY: 0.347 AC XY: 25777 AN XY: 74278

African (AFR) AF: 0.244 AC: 10110 AN: 41488

American (AMR) AF: 0.342 AC: 5219 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1114 AN: 5158

South Asian (SAS) AF: 0.289 AC: 1388 AN: 4800

European-Finnish (FIN) AF: 0.465 AC: 4903 AN: 10552

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27250 AN: 67964

Other (OTH) AF: 0.351 AC: 740 AN: 2106

Alfa AF: 0.375 Hom.: 34203

Bravo AF: 0.335

Asia WGS AF: 0.248 AC: 863 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	0.011
DANN	Benign	0.65
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12407028; hg19: chr1-68647716; COSMIC: COSV52038818; COSMIC: COSV52038818;