rs4738899

Variant names:

• chr8-61492838-G-A
• rs4738899
• NM_173519.3:c.978-6617G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173519.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLVS1	NM_173519.3	MANE Select	c.978-6617G>A		intron	N/A	NP_775790.1	Q8IUQ0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLVS1	ENST00000325897.5	TSL:1 MANE Select	c.978-6617G>A		intron	N/A	ENSP00000325506.4	Q8IUQ0-1
	CLVS1	ENST00000518592.5	TSL:1	c.141-6617G>A		intron	N/A	ENSP00000429869.1	G3V122
	CLVS1	ENST00000519846.5	TSL:5	c.978-6617G>A		intron	N/A	ENSP00000428402.1	Q8IUQ0-1

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

African (AFR) AF: 0.203 AC: 8415 AN: 41410

American (AMR) AF: 0.593 AC: 9054 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2476 AN: 5162

South Asian (SAS) AF: 0.652 AC: 3136 AN: 4810

European-Finnish (FIN) AF: 0.720 AC: 7605 AN: 10566

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48271 AN: 67984

Other (OTH) AF: 0.563 AC: 1189 AN: 2112

Alfa AF: 0.651 Hom.: 105187

Bravo AF: 0.522

Asia WGS AF: 0.569 AC: 1976 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4738899; hg19: chr8-62405397; COSMIC: COSV107354229;