rs10504324

chr8-61235414-G-A

Variant summary

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

The ENST00000522621.1(CLVS1):c.-151-64263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,206 control chromosomes in the GnomAD database, including 1,048 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 0.085 (1048 hom., cov: 33)
• Consequence: CLVS1 ENST00000522621.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLVS1	XM_017013141.2	c.-151-64263G>A		intron_variant
CLVS1	XM_024447079.2	c.-288-56904G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLVS1	ENST00000522621.1	c.-151-64263G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12873 AN: 152088 Hom.: 1050 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0357

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0626

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

GnomAD4 genome AF: 0.0847 AC: 12899 AN: 152206 Hom.: 1048 Cov.: 33 AF XY: 0.0823 AC XY: 6124 AN XY: 74422

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0356

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.0428 Hom.: 404

Bravo AF: 0.0907

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.2
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10504324; hg19: chr8-62147973;