rs4367528

Positions:

• chr8-61465382-C-T

Variant summary

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

The NM_173519.3(CLVS1):​c.977+6840C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,104 control chromosomes in the GnomAD database, including 57,260 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 0.87 (57256 hom., cov: 30)
  • Exomes 𝑓: 1.0 (4 hom.)
• Consequence: CLVS1 NM_173519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLVS1	NM_173519.3	c.977+6840C>T		intron_variant		ENST00000325897.5	NP_775790.1
CLVS1	XM_017013141.2	c.977+6840C>T		intron_variant			XP_016868630.1
CLVS1	XM_017013142.3	c.977+6840C>T		intron_variant			XP_016868631.1
CLVS1	XM_024447079.2	c.977+6840C>T		intron_variant			XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000325897.5	c.977+6840C>T		intron_variant		1	NM_173519.3	ENSP00000325506	P1

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131603 AN: 151978 Hom.: 57204 Cov.: 30

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.866

GnomAD4 exome AF: 1.00 AC: 8 AN: 8 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.866 AC: 131710 AN: 152096 Hom.: 57256 Cov.: 30 AF XY: 0.863 AC XY: 64176 AN XY: 74348

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.868

Alfa AF: 0.894 Hom.: 30413

Bravo AF: 0.861

Asia WGS AF: 0.862 AC: 2998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0070
DANN	Benign	0.53

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: rs4367528; hg19: chr8-62377941;