chr7-116482791-A-G

Variant names:

• chr7-116482791-A-G
• rs6975771
• ENST00000462876.5:n.1007-14978A>G

Variant summary

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

The NR_188013.1(CAV2-DT):​n.49T>C 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 0.838 in 152,258 control chromosomes in the GnomAD database, including 53,661 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 0.84 (53645 hom., cov: 32)
  • Exomes 𝑓: 0.79 (16 hom.)
• Consequence: CAV2-DT NR_188013.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 2 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

CAV2-DT (HGNC:40129):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_188013.1. 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_188013.1		n.49T>C		non_coding_transcript_exon	Exon 1 of 4
	CAV2-DT	NR_188009.1		n.254+22T>C		intron	N/A
	CAV2-DT	NR_188010.1		n.163+16563T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2	ENST00000462876.5	TSL:1	n.1007-14978A>G		intron	N/A
	CAV2	ENST00000467035.5	TSL:1	n.753-14978A>G		intron	N/A
	CAV2	ENST00000472470.5	TSL:1	n.407-14978A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127492 AN: 152084 Hom.: 53606 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.844

GnomAD4 exome AF: 0.786 AC: 44 AN: 56 Hom.: 16 Cov.: 0 AF XY: 0.833 AC XY: 35 AN XY: 42

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.795 AC: 35 AN: 44

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.838 AC: 127589 AN: 152202 Hom.: 53645 Cov.: 32 AF XY: 0.842 AC XY: 62639 AN XY: 74422

African (AFR) AF: 0.793 AC: 32909 AN: 41498

American (AMR) AF: 0.867 AC: 13269 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3016 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4898 AN: 5178

South Asian (SAS) AF: 0.866 AC: 4178 AN: 4824

European-Finnish (FIN) AF: 0.878 AC: 9309 AN: 10606

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57227 AN: 68008

Other (OTH) AF: 0.844 AC: 1786 AN: 2116

Alfa AF: 0.842 Hom.: 230592

Bravo AF: 0.836

Asia WGS AF: 0.893 AC: 3103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.66
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs6975771; hg19: chr7-116122845;