Genetic Variant CLVS1:c.977+159C>T (chr8-61458701-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173519.3(CLVS1):c.977+159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 575,490 control chromosomes in the GnomAD database, including 162,004 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 0.63 ( 34472 hom., cov: 32)

Exomes 𝑓: 0.77 ( 127532 hom. )

Consequence

CLVS1
NM_173519.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.192

Variant links:

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]

CLVS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLVS1	NM_173519.3 link	c.977+159C>T	intron_variant	Intron 5 of 5	ENST00000325897.5	NP_775790.1
CLVS1	XM_017013141.2 link	c.977+159C>T	intron_variant	Intron 6 of 6		XP_016868630.1	Q8IUQ0-1
CLVS1	XM_017013142.3 link	c.977+159C>T	intron_variant	Intron 6 of 6		XP_016868631.1	Q8IUQ0-1
CLVS1	XM_024447079.2 link	c.977+159C>T	intron_variant	Intron 8 of 8		XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000325897.5 link	c.977+159C>T		intron_variant	Intron 5 of 5	1	NM_173519.3	ENSP00000325506.4		Q8IUQ0-1

Frequencies

GnomAD3 genomes

AF:

0.631

AC:

95878

AN:

151922

Hom.:

34464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.840

Gnomad AMR

AF:

0.709

Gnomad ASJ

AF:

0.768

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.745

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.794

Gnomad OTH

AF:

0.657

GnomAD4 exome

AF:

0.769

AC:

325763

AN:

423450

Hom.:

127532

Cov.:

AF XY:

0.772

AC XY:

170599

AN XY:

220898

show subpopulations

Gnomad4 AFR exome

AF:

0.252

Gnomad4 AMR exome

AF:

0.726

Gnomad4 ASJ exome

AF:

0.780

Gnomad4 EAS exome

AF:

0.790

Gnomad4 SAS exome

AF:

0.767

Gnomad4 FIN exome

AF:

0.759

Gnomad4 NFE exome

AF:

0.796

Gnomad4 OTH exome

AF:

0.740

GnomAD4 genome

AF:

0.631

AC:

95893

AN:

152040

Hom.:

34472

Cov.:

AF XY:

0.631

AC XY:

46850

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.710

Gnomad4 ASJ

AF:

0.768

Gnomad4 EAS

AF:

0.756

Gnomad4 SAS

AF:

0.766

Gnomad4 FIN

AF:

0.745

Gnomad4 NFE

AF:

0.794

Gnomad4 OTH

AF:

0.657

Alfa

AF:

0.776

Hom.:

91298

Bravo

AF:

0.611

Asia WGS

AF:

0.716

AC:

2493

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over