Genetic Variant ENST00000462876.5:n.1007-14978A>G (chr7-116482791-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 ENST00000462876.5(CAV2):n.1007-14978A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,258 control chromosomes in the GnomAD database, including 53,661 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 0.84 ( 53645 hom., cov: 32)

Exomes 𝑓: 0.79 ( 16 hom. )

Consequence

CAV2
ENST00000462876.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.266

Publications

2 publications found

Variant links:

Genes affected

CAV2 (HGNC:1528): (caveolin 2) The protein encoded by this gene is a major component of the inner surface of caveolae, small invaginations of the plasma membrane, and is involved in essential cellular functions, including signal transduction, lipid metabolism, cellular growth control and apoptosis. This protein may function as a tumor suppressor. This gene and related family member (CAV1) are located next to each other on chromosome 7, and express colocalizing proteins that form a stable hetero-oligomeric complex. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Additional isoforms resulting from the use of alternate in-frame translation initiation codons have also been described, and shown to have preferential localization in the cell (PMID:11238462). [provided by RefSeq, May 2011]

CAV2 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CAV2 links:

ENSG00000237813 (HGNC:40129):

ENSG00000237813 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 (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CAV2-DT	NR_188013.1 link	n.49T>C	non_coding_transcript_exon_variant	Exon 1 of 4
CAV2-DT	NR_188009.1 link	n.254+22T>C	intron_variant	Intron 2 of 3
CAV2-DT	NR_188010.1 link	n.163+16563T>C	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CAV2	ENST00000462876.5 link	n.1007-14978A>G	intron_variant	Intron 8 of 13	1
CAV2	ENST00000467035.5 link	n.753-14978A>G	intron_variant	Intron 6 of 8	1
CAV2	ENST00000472470.5 link	n.407-14978A>G	intron_variant	Intron 3 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

127492

AN:

152084

Hom.:

53606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.867

Gnomad ASJ

AF:

0.869

Gnomad EAS

AF:

0.946

Gnomad SAS

AF:

0.866

Gnomad FIN

AF:

0.878

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.841

Gnomad OTH

AF:

0.844

GnomAD4 exome

AF:

0.786

AC:

AN:

Hom.:

Cov.:

AF XY:

0.833

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.795

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.838

AC:

127589

AN:

152202

Hom.:

53645

Cov.:

AF XY:

0.842

AC XY:

62639

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.793

AC:

32909

AN:

41498

American (AMR)

AF:

0.867

AC:

13269

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.869

AC:

3016

AN:

3470

East Asian (EAS)

AF:

0.946

AC:

4898

AN:

5178

South Asian (SAS)

AF:

0.866

AC:

4178

AN:

4824

European-Finnish (FIN)

AF:

0.878

AC:

9309

AN:

10606

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.841

AC:

57227

AN:

68008

Other (OTH)

AF:

0.844

AC:

1786

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1031

2061

3092

4122

5153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.842

Hom.:

230592

Bravo

AF:

0.836

Asia WGS

AF:

0.893

AC:

3103

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

3.2

(source)

DANN

Benign

0.66

PhyloP100

0.27

Splicing

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

Publications

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ENST00000462876.5:n.1007-14978A>G

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