8-61090894-A-G

Variant names:

• chr8-61090894-A-G
• rs1367972
• ENST00000522621.1:c.-243+33664A>G

Variant summary

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

The ENST00000522621.1(CLVS1):​c.-243+33664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 517,940 control chromosomes in the GnomAD database, including 84,082 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 0.57 (24846 hom., cov: 31)
  • Exomes 𝑓: 0.57 (59236 hom.)
• Consequence: CLVS1 ENST00000522621.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 11 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522621.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLVS1	ENST00000522621.1	TSL:4	c.-243+33664A>G		intron	N/A	ENSP00000428986.1	E5RK22

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86426 AN: 151752 Hom.: 24825 Cov.: 31

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.609

GnomAD2 exomes AF: 0.568 AC: 130024 AN: 228788 AF XY: 0.567

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.634

Gnomad ASJ exome AF: 0.639

Gnomad EAS exome AF: 0.472

Gnomad FIN exome AF: 0.504

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.566 AC: 207106 AN: 366070 Hom.: 59236 Cov.: 0 AF XY: 0.563 AC XY: 118212 AN XY: 209938

African (AFR) AF: 0.573 AC: 6004 AN: 10472

American (AMR) AF: 0.635 AC: 22991 AN: 36184

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 7495 AN: 11700

East Asian (EAS) AF: 0.472 AC: 6209 AN: 13156

South Asian (SAS) AF: 0.551 AC: 36727 AN: 66650

European-Finnish (FIN) AF: 0.506 AC: 8545 AN: 16874

Middle Eastern (MID) AF: 0.661 AC: 1885 AN: 2850

European-Non Finnish (NFE) AF: 0.564 AC: 107981 AN: 191600

Other (OTH) AF: 0.559 AC: 9269 AN: 16584

GnomAD4 genome AF: 0.569 AC: 86485 AN: 151870 Hom.: 24846 Cov.: 31 AF XY: 0.568 AC XY: 42150 AN XY: 74210

African (AFR) AF: 0.572 AC: 23670 AN: 41386

American (AMR) AF: 0.639 AC: 9774 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2266 AN: 3468

East Asian (EAS) AF: 0.483 AC: 2488 AN: 5148

South Asian (SAS) AF: 0.558 AC: 2681 AN: 4808

European-Finnish (FIN) AF: 0.504 AC: 5299 AN: 10524

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.564 AC: 38285 AN: 67936

Other (OTH) AF: 0.603 AC: 1272 AN: 2110

Alfa AF: 0.565 Hom.: 89103

Bravo AF: 0.582

Asia WGS AF: 0.518 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs1367972; hg19: chr8-62003453;