chr7-116330568-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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

ENSG00000237813 (HGNC:40129):

LOC105375463 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462876.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2	ENST00000462876.5	TSL:1	n.470-6552G>T		intron	N/A
	CAV2	ENST00000467035.5	TSL:1	n.295-9255G>T		intron	N/A
	CAV2	ENST00000472470.5	TSL:1	n.241+40518G>T		intron	N/A

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

African (AFR) AF: 0.420 AC: 17388 AN: 41424

American (AMR) AF: 0.248 AC: 3789 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1420 AN: 3466

East Asian (EAS) AF: 0.0690 AC: 357 AN: 5176

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4812

European-Finnish (FIN) AF: 0.228 AC: 2413 AN: 10576

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21995 AN: 67954

Other (OTH) AF: 0.337 AC: 712 AN: 2114

Alfa AF: 0.328 Hom.: 10913

Bravo AF: 0.331

Asia WGS AF: 0.183 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.44
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs12154695; hg19: chr7-115970622;