8-61496869-G-T

Variant names:

• chr8-61496869-G-T
• rs903027
• NM_173519.3:c.978-2586G>T

Variant summary

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

The ENST00000325897.5(CLVS1):​c.978-2586G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,144 control chromosomes in the GnomAD database, including 52,832 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 0.83 (52832 hom., cov: 32)
• Consequence: CLVS1 ENST00000325897.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000325897.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLVS1	NM_173519.3	MANE Select	c.978-2586G>T		intron	N/A	NP_775790.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLVS1	ENST00000325897.5	TSL:1 MANE Select	c.978-2586G>T		intron	N/A	ENSP00000325506.4
	CLVS1	ENST00000518592.5	TSL:1	c.141-2586G>T		intron	N/A	ENSP00000429869.1
	CLVS1	ENST00000519846.5	TSL:5	c.978-2586G>T		intron	N/A	ENSP00000428402.1

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126295 AN: 152026 Hom.: 52775 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.831 AC: 126405 AN: 152144 Hom.: 52832 Cov.: 32 AF XY: 0.829 AC XY: 61682 AN XY: 74392

African (AFR) AF: 0.817 AC: 33890 AN: 41492

American (AMR) AF: 0.768 AC: 11737 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2796 AN: 3472

East Asian (EAS) AF: 0.602 AC: 3098 AN: 5146

South Asian (SAS) AF: 0.806 AC: 3891 AN: 4826

European-Finnish (FIN) AF: 0.905 AC: 9586 AN: 10594

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58596 AN: 68016

Other (OTH) AF: 0.817 AC: 1725 AN: 2112

Alfa AF: 0.839 Hom.: 121698

Bravo AF: 0.818

Asia WGS AF: 0.745 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.48
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs903027; hg19: chr8-62409428; COSMIC: COSV57977983; COSMIC: COSV57977983;