Genetic Variant ENST00000522621.1:c.-243+33664A>G (chr8-61090894-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000522621.1(CLVS1):c.-243+33664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 517,940 control chromosomes in the GnomAD database, including 84,082 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 0.57 ( 24846 hom., cov: 31)

Exomes 𝑓: 0.57 ( 59236 hom. )

Consequence

CLVS1
ENST00000522621.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.120

Publications

11 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLVS1	XM_017013141.2 link	c.-243+33664A>G		intron_variant	Intron 1 of 6		XP_016868630.1	Q8IUQ0-1
CLVS1	XM_024447079.2 link	c.-379-40876A>G		intron_variant	Intron 2 of 8		XP_024302847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLVS1	ENST00000522621.1 link	c.-243+33664A>G		intron_variant	Intron 1 of 2	4		ENSP00000428986.1		E5RK22

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86426

AN:

151752

Hom.:

24825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.558

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.669

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.609

GnomAD2 exomes

AF:

0.568

AC:

130024

AN:

228788

AF XY:

0.567

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.634

Gnomad ASJ exome

AF:

0.639

Gnomad EAS exome

AF:

0.472

Gnomad FIN exome

AF:

0.504

Gnomad NFE exome

AF:

0.567

Gnomad OTH exome

AF:

0.575

GnomAD4 exome

AF:

0.566

AC:

207106

AN:

366070

Hom.:

59236

Cov.:

AF XY:

0.563

AC XY:

118212

AN XY:

209938

show subpopulations

African (AFR)

AF:

0.573

AC:

6004

AN:

10472

American (AMR)

AF:

0.635

AC:

22991

AN:

36184

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

7495

AN:

11700

East Asian (EAS)

AF:

0.472

AC:

6209

AN:

13156

South Asian (SAS)

AF:

0.551

AC:

36727

AN:

66650

European-Finnish (FIN)

AF:

0.506

AC:

8545

AN:

16874

Middle Eastern (MID)

AF:

0.661

AC:

1885

AN:

2850

European-Non Finnish (NFE)

AF:

0.564

AC:

107981

AN:

191600

Other (OTH)

AF:

0.559

AC:

9269

AN:

16584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

4596

9193

13789

18386

22982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.569

AC:

86485

AN:

151870

Hom.:

24846

Cov.:

AF XY:

0.568

AC XY:

42150

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.572

AC:

23670

AN:

41386

American (AMR)

AF:

0.639

AC:

9774

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.653

AC:

2266

AN:

3468

East Asian (EAS)

AF:

0.483

AC:

2488

AN:

5148

South Asian (SAS)

AF:

0.558

AC:

2681

AN:

4808

European-Finnish (FIN)

AF:

0.504

AC:

5299

AN:

10524

Middle Eastern (MID)

AF:

0.668

AC:

195

AN:

292

European-Non Finnish (NFE)

AF:

0.564

AC:

38285

AN:

67936

Other (OTH)

AF:

0.603

AC:

1272

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1874

3748

5621

7495

9369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.565

Hom.:

89103

Bravo

AF:

0.582

Asia WGS

AF:

0.518

AC:

1802

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.9

(source)

DANN

Benign

0.59

PhyloP100

0.12

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over