Genetic Variant ENST00000462876.5:n.1076T>G (chr7-116497838-T-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.1076T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,232 control chromosomes in the GnomAD database, including 1,919 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 0.15 ( 1918 hom., cov: 33)

Exomes 𝑓: 0.33 ( 1 hom. )

Consequence

CAV2
ENST00000462876.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Publications

7 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:

CAV2-DT (HGNC:40129):

CAV2-DT links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462876.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
CAV2-DT	NR_188009.1	n.163+1516A>C	intron	N/A
CAV2-DT	NR_188010.1	n.163+1516A>C	intron	N/A
CAV2-DT	NR_188011.1	n.163+1516A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CAV2	ENST00000462876.5	TSL:1	n.1076T>G	non_coding_transcript_exon	Exon 9 of 14
CAV2	ENST00000467035.5	TSL:1	n.822T>G	non_coding_transcript_exon	Exon 7 of 9
CAV2	ENST00000472470.5	TSL:1	n.476T>G	non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23252

AN:

152108

Hom.:

1919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.0653

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.153

AC:

23262

AN:

152226

Hom.:

1918

Cov.:

AF XY:

0.148

AC XY:

11044

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.147

AC:

6108

AN:

41518

American (AMR)

AF:

0.144

AC:

2198

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

900

AN:

3470

East Asian (EAS)

AF:

0.0102

AC:

AN:

5180

South Asian (SAS)

AF:

0.177

AC:

852

AN:

4824

European-Finnish (FIN)

AF:

0.0653

AC:

693

AN:

10616

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11881

AN:

68012

Other (OTH)

AF:

0.172

AC:

363

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1012

2024

3035

4047

5059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.178

Hom.:

4236

Bravo

AF:

0.158

Asia WGS

AF:

0.0790

AC:

277

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.72

(source)

DANN

Benign

0.77

PhyloP100

-1.6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over