chr1-68199340-T-C

Variant names:

• chr1-68199340-T-C
• rs7554551
• NM_024911.7:c.107-5113A>G

Variant summary

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

The NM_001002292.4(WLS):​c.107-5119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,934 control chromosomes in the GnomAD database, including 6,997 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 0.30 (6997 hom., cov: 31)
• Consequence: WLS NM_001002292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002292.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	NM_024911.7	MANE Select	c.107-5113A>G		intron	N/A	NP_079187.3
	WLS	NM_001002292.4		c.107-5119A>G		intron	N/A	NP_001002292.3
	WLS	NM_001193334.1		c.106+32854A>G		intron	N/A	NP_001180263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WLS	ENST00000262348.9	TSL:1 MANE Select	c.107-5113A>G		intron	N/A	ENSP00000262348.4
	WLS	ENST00000354777.6	TSL:1	c.107-5119A>G		intron	N/A	ENSP00000346829.2
	WLS	ENST00000370976.7	TSL:1	c.106+32854A>G		intron	N/A	ENSP00000360015.3

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45090 AN: 151814 Hom.: 6997 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.297 AC: 45098 AN: 151934 Hom.: 6997 Cov.: 31 AF XY: 0.297 AC XY: 22041 AN XY: 74236

African (AFR) AF: 0.198 AC: 8190 AN: 41452

American (AMR) AF: 0.347 AC: 5290 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3470

East Asian (EAS) AF: 0.219 AC: 1130 AN: 5152

South Asian (SAS) AF: 0.329 AC: 1584 AN: 4808

European-Finnish (FIN) AF: 0.313 AC: 3291 AN: 10528

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23200 AN: 67950

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.326 Hom.: 18838

Bravo AF: 0.293

Asia WGS AF: 0.315 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.1
DANN	Benign	0.74
PhyloP100		-0.31
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: rs7554551; hg19: chr1-68665023;