7-116330568-G-T

Variant names:

• chr7-116330568-G-T
• rs12154695
• ENST00000462876.5:n.470-6552G>T

Variant summary

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

The ENST00000462876.5(CAV2):​n.470-6552G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,994 control chromosomes in the GnomAD database, including 8,735 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 0.33 (8735 hom., cov: 32)
• Consequence: CAV2 ENST00000462876.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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]

ENSG00000237813 (HGNC:40129):

LOC105375463 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375463	XR_001745329.2	n.966-6552G>T		intron_variant	Intron 5 of 5
LOC105375463	XR_001745332.2	n.827-6552G>T		intron_variant	Intron 6 of 6
LOC105375463	XR_001745335.2	n.565-6552G>T		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV2	ENST00000462876.5	n.470-6552G>T		intron_variant	Intron 4 of 13	1
CAV2	ENST00000467035.5	n.295-9255G>T		intron_variant	Intron 3 of 8	1
CAV2	ENST00000472470.5	n.241+40518G>T		intron_variant	Intron 2 of 5	1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49752 AN: 151876 Hom.: 8735 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.327 AC: 49763 AN: 151994 Hom.: 8735 Cov.: 32 AF XY: 0.319 AC XY: 23681 AN XY: 74298

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.0690

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.337

Alfa AF: 0.326 Hom.: 8242

Bravo AF: 0.331

Asia WGS AF: 0.183 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12154695; hg19: chr7-115970622;