rs6976316

Variant names:

• chr7-116482889-G-A
• rs6976316
• ENST00000462876.5:n.1007-14880G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-116482889-G-A
• chr7-116482889-G-C
• chr7-116482889-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000462876.5(CAV2):​n.1007-14880G>A variant causes a intron 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: CAV2 ENST00000462876.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458
• Publications: 9 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):

ACMG classification

Our verdict: Benign. The variant received -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.

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
	CAV2-DT	NR_188009.1		n.178C>T		non_coding_transcript_exon	Exon 2 of 4
	CAV2-DT	NR_188011.1		n.178C>T		non_coding_transcript_exon	Exon 2 of 5
	CAV2-DT	NR_188010.1		n.163+16465C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2	ENST00000462876.5	TSL:1	n.1007-14880G>A		intron	N/A
	CAV2	ENST00000467035.5	TSL:1	n.753-14880G>A		intron	N/A
	CAV2	ENST00000472470.5	TSL:1	n.407-14880G>A		intron	N/A

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

African (AFR) AF: 1.00 AC: 2 AN: 2

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.421 AC: 16 AN: 38

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.406 AC: 16817 AN: 41406

American (AMR) AF: 0.576 AC: 8799 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1697 AN: 3464

East Asian (EAS) AF: 0.773 AC: 3984 AN: 5154

South Asian (SAS) AF: 0.555 AC: 2666 AN: 4804

European-Finnish (FIN) AF: 0.570 AC: 6025 AN: 10566

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35197 AN: 67952

Other (OTH) AF: 0.520 AC: 1095 AN: 2106

Alfa AF: 0.501 Hom.: 12093

Bravo AF: 0.499

Asia WGS AF: 0.684 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.72
PhyloP100		0.46

Splicing

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

Other links and lift over

dbSNP: rs6976316; hg19: chr7-116122943;