chr7-116482889-G-A

Position:

• chr7-116482889-G-A

Variant summary

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

The ENST00000446355.2(ENSG00000237813):​n.127C>T 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 0.506 in 151,974 control chromosomes in the GnomAD database, including 20,044 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 0.51 (20039 hom., cov: 31)
  • Exomes 𝑓: 0.43 (5 hom.)
• Consequence: ENST00000446355.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 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.127C>T		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76851 AN: 151812 Hom.: 20022 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.432 AC: 19 AN: 44 Hom.: 5 Cov.: 0 AF XY: 0.471 AC XY: 16 AN XY: 34

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.421

GnomAD4 genome AF: 0.506 AC: 76897 AN: 151930 Hom.: 20039 Cov.: 31 AF XY: 0.513 AC XY: 38076 AN XY: 74262

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.520

Alfa AF: 0.491 Hom.: 7572

Bravo AF: 0.499

Asia WGS AF: 0.684 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6976316; hg19: chr7-116122943;