rs4727833

chr7-116507854-C-Gchr7-116507854-C-T

Variant summary

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

The NM_001233.5(CAV2):c.*1733C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,858 control chromosomes in the GnomAD database, including 18,956 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 0.49 (18956 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CAV2 NM_001233.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV2	NM_001233.5	c.*1733C>G		3_prime_UTR_variant	3/3	ENST00000222693.5
CAV2	NM_001206747.2	c.*1733C>G		3_prime_UTR_variant	3/3
CAV2	NM_001206748.2	c.*1733C>G		3_prime_UTR_variant	2/2
CAV2	NM_198212.3	c.*1695C>G		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV2	ENST00000222693.5	c.*1733C>G		3_prime_UTR_variant	3/3	1	NM_001233.5	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74639 AN: 151740 Hom.: 18934 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.497

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.492 AC: 74703 AN: 151858 Hom.: 18956 Cov.: 32 AF XY: 0.500 AC XY: 37121 AN XY: 74206

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.501

Alfa AF: 0.383 Hom.: 1140

Bravo AF: 0.484

Asia WGS AF: 0.679 AC: 2357 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.41
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4727833; hg19: chr7-116147908;