rs12530912

Variant names:

• chr7-116487475-T-G
• rs12530912
• ENST00000462876.5:n.1007-10294T>G

Variant summary

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

The ENST00000462876.5(CAV2):​n.1007-10294T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,190 control chromosomes in the GnomAD database, including 4,932 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 0.25 (4932 hom., cov: 33)
• Consequence: CAV2 ENST00000462876.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 8 publications found

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

ENSG00000237813 (HGNC:40129):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV2-DT	NR_188009.1	n.164-4572A>C		intron_variant	Intron 1 of 3
CAV2-DT	NR_188010.1	n.163+11879A>C		intron_variant	Intron 1 of 3
CAV2-DT	NR_188011.1	n.164-4572A>C		intron_variant	Intron 1 of 4
CAV2-DT	NR_188012.1	n.163+11879A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV2	ENST00000462876.5	n.1007-10294T>G		intron_variant	Intron 8 of 13	1
CAV2	ENST00000467035.5	n.753-10294T>G		intron_variant	Intron 6 of 8	1
CAV2	ENST00000472470.5	n.407-10294T>G		intron_variant	Intron 3 of 5	1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38295 AN: 152072 Hom.: 4924 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.252 AC: 38329 AN: 152190 Hom.: 4932 Cov.: 33 AF XY: 0.253 AC XY: 18807 AN XY: 74402

African (AFR) AF: 0.283 AC: 11754 AN: 41502

American (AMR) AF: 0.235 AC: 3594 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3468

East Asian (EAS) AF: 0.172 AC: 891 AN: 5178

South Asian (SAS) AF: 0.291 AC: 1406 AN: 4830

European-Finnish (FIN) AF: 0.242 AC: 2564 AN: 10580

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16353 AN: 68012

Other (OTH) AF: 0.236 AC: 499 AN: 2116

Alfa AF: 0.247 Hom.: 2482

Bravo AF: 0.254

Asia WGS AF: 0.192 AC: 670 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.74
PhyloP100		0.55

Splicing

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

Other links and lift over

dbSNP: rs12530912; hg19: chr7-116127529;