rs2083437

Variant names:

• chr8-61417465-G-C
• rs2083437
• NM_173519.3:c.631-36676G>C

Variant summary

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

The NM_173519.3(CLVS1):​c.631-36676G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,080 control chromosomes in the GnomAD database, including 2,879 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 0.11 (2879 hom., cov: 32)
• Consequence: CLVS1 NM_173519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLVS1	NM_173519.3	c.631-36676G>C		intron_variant	Intron 3 of 5	ENST00000325897.5	NP_775790.1
CLVS1	XM_017013141.2	c.631-36676G>C		intron_variant	Intron 4 of 6		XP_016868630.1
CLVS1	XM_017013142.3	c.631-36676G>C		intron_variant	Intron 4 of 6		XP_016868631.1
CLVS1	XM_024447079.2	c.631-36676G>C		intron_variant	Intron 6 of 8		XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000325897.5	c.631-36676G>C		intron_variant	Intron 3 of 5	1	NM_173519.3	ENSP00000325506.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16764 AN: 151962 Hom.: 2880 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.00689

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00340

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.110 AC: 16795 AN: 152080 Hom.: 2879 Cov.: 32 AF XY: 0.108 AC XY: 8019 AN XY: 74336

African (AFR) AF: 0.364 AC: 15089 AN: 41412

American (AMR) AF: 0.0412 AC: 629 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.0689 AC: 356 AN: 5164

South Asian (SAS) AF: 0.0380 AC: 183 AN: 4822

European-Finnish (FIN) AF: 0.00689 AC: 73 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00340 AC: 231 AN: 68012

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.0696 Hom.: 218

Bravo AF: 0.125

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.79
DANN	Benign	0.50
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2083437; hg19: chr8-62330024;