8-61090894-A-G

Position:

• chr8-61090894-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLVS1	XM_017013141.2	c.-243+33664A>G		intron_variant			XP_016868630.1
CLVS1	XM_024447079.2	c.-379-40876A>G		intron_variant			XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000522621.1	c.-243+33664A>G		intron_variant		4		ENSP00000428986.1

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

GnomAD3 exomes AF: 0.568 AC: 130024 AN: 228788 Hom.: 37435 AF XY: 0.567 AC XY: 71670 AN XY: 126466

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 SAS exome AF: 0.554

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

Gnomad4 AFR exome AF: 0.573

Gnomad4 AMR exome AF: 0.635

Gnomad4 ASJ exome AF: 0.641

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.559

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

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.603

Alfa AF: 0.565 Hom.: 41106

Bravo AF: 0.582

Asia WGS AF: 0.518 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1367972; hg19: chr8-62003453;