chr8-61301934-T-C

Variant names:

• chr8-61301934-T-C
• rs2919303
• NM_173519.3:c.455+1652T>C

Variant summary

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

The NM_173519.3(CLVS1):​c.455+1652T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,104 control chromosomes in the GnomAD database, including 33,039 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 0.64 (33039 hom., cov: 32)
• Consequence: CLVS1 NM_173519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLVS1	NM_173519.3	c.455+1652T>C		intron_variant	Intron 2 of 5	ENST00000325897.5	NP_775790.1
CLVS1	XM_017013141.2	c.455+1652T>C		intron_variant	Intron 3 of 6		XP_016868630.1
CLVS1	XM_017013142.3	c.455+1652T>C		intron_variant	Intron 3 of 6		XP_016868631.1
CLVS1	XM_024447079.2	c.455+1652T>C		intron_variant	Intron 5 of 8		XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000325897.5	c.455+1652T>C		intron_variant	Intron 2 of 5	1	NM_173519.3	ENSP00000325506.4
CLVS1	ENST00000518592.5	c.-383+13796T>C		intron_variant	Intron 1 of 4	1		ENSP00000429869.1
CLVS1	ENST00000519846.5	c.455+1652T>C		intron_variant	Intron 3 of 6	5		ENSP00000428402.1
CLVS1	ENST00000521189.1	n.761+1656T>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97859 AN: 151984 Hom.: 32974 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.644 AC: 97987 AN: 152104 Hom.: 33039 Cov.: 32 AF XY: 0.657 AC XY: 48837 AN XY: 74358

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.620

Alfa AF: 0.548 Hom.: 30608

Bravo AF: 0.647

Asia WGS AF: 0.883 AC: 3067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.61
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: rs2919303; hg19: chr8-62214493;