7-116482791-A-G

Variant summary

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

The ENST00000446355.2(ENSG00000237813):n.203+22T>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 0.838 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: ENST00000446355.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 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.203+22T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127492 AN: 152084 Hom.: 53606 Cov.: 32

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: 44 AN: 56 Hom.: 16 Cov.: 0 AF XY: 0.833 AC XY: 35 AN XY: 42

Gnomad4 AFR exome AF: 0.750

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.795

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.838 AC: 127589 AN: 152202 Hom.: 53645 Cov.: 32 AF XY: 0.842 AC XY: 62639 AN XY: 74422

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.844

Alfa AF: 0.846 Hom.: 109932

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
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6975771; hg19: chr7-116122845;