rs12530912

Positions:

• chr7-116487475-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000446355.2(ENSG00000237813):​n.113-4572A>C variant causes a intron, non coding transcript 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: ENST00000446355.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000446355.2	n.113-4572A>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.236

Alfa AF: 0.247 Hom.: 2242

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12530912; hg19: chr7-116127529;