rs12681792

Positions:

• chr8-61141904-C-A

Variant summary

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

The ENST00000522621.1(CLVS1):​c.-152+10044C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,060 control chromosomes in the GnomAD database, including 4,479 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 0.23 (4479 hom., cov: 32)
• Consequence: CLVS1 ENST00000522621.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

Genes affected

CLVS1 (HGNC:23139): (clavesin 1) Enables phosphatidylinositol-3,5-bisphosphate binding activity. Predicted to be involved in lysosome organization. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLVS1	XM_017013141.2	c.-152+10044C>A		intron_variant			XP_016868630.1
CLVS1	XM_024447079.2	c.-289+10044C>A		intron_variant			XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000522621.1	c.-152+10044C>A		intron_variant		4		ENSP00000428986

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35224 AN: 151942 Hom.: 4474 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.232 AC: 35243 AN: 152060 Hom.: 4479 Cov.: 32 AF XY: 0.236 AC XY: 17555 AN XY: 74320

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0799

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.188

Alfa AF: 0.208 Hom.: 718

Bravo AF: 0.220

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12681792; hg19: chr8-62054463;