rs4738899

Positions:

• chr8-61492838-G-A

Variant summary

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

The NM_173519.3(CLVS1):​c.978-6617G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,982 control chromosomes in the GnomAD database, including 26,487 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 0.55 (26487 hom., cov: 32)
• Consequence: CLVS1 NM_173519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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]

CLVS1 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLVS1	NM_173519.3	c.978-6617G>A		intron_variant		ENST00000325897.5	NP_775790.1
CLVS1	XM_017013141.2	c.978-6617G>A		intron_variant			XP_016868630.1
CLVS1	XM_017013142.3	c.978-6617G>A		intron_variant			XP_016868631.1
CLVS1	XM_024447079.2	c.978-6617G>A		intron_variant			XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000325897.5	c.978-6617G>A		intron_variant		1	NM_173519.3	ENSP00000325506.4

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83155 AN: 151862 Hom.: 26473 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.547 AC: 83179 AN: 151982 Hom.: 26487 Cov.: 32 AF XY: 0.548 AC XY: 40722 AN XY: 74278

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.563

Alfa AF: 0.681 Hom.: 70026

Bravo AF: 0.522

Asia WGS AF: 0.569 AC: 1976 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs4738899; hg19: chr8-62405397;