7-116507854-C-G

Variant names:

• chr7-116507854-C-G
• rs4727833
• NM_001233.5:c.*1733C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

CAV2 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001233.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2	NM_001233.5	MANE Select	c.*1733C>G		3_prime_UTR	Exon 3 of 3	NP_001224.1	Q53X57
	CAV2	NM_001206747.2		c.*1733C>G		3_prime_UTR	Exon 3 of 3	NP_001193676.1	P51636-2
	CAV2	NM_198212.3		c.*1695C>G		3_prime_UTR	Exon 2 of 2	NP_937855.1	P51636-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2	ENST00000222693.5	TSL:1 MANE Select	c.*1733C>G		3_prime_UTR	Exon 3 of 3	ENSP00000222693.4	P51636-1
	CAV2	ENST00000892151.1		c.*1733C>G		downstream_gene	N/A	ENSP00000562210.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.392 AC: 16210 AN: 41376

American (AMR) AF: 0.561 AC: 8569 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1686 AN: 3472

East Asian (EAS) AF: 0.774 AC: 4004 AN: 5176

South Asian (SAS) AF: 0.549 AC: 2641 AN: 4814

European-Finnish (FIN) AF: 0.568 AC: 5970 AN: 10512

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34045 AN: 67924

Other (OTH) AF: 0.501 AC: 1059 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.41
DANN	Benign	0.46
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4727833; hg19: chr7-116147908;