rs17138767

Positions:

• chr7-116497623-A-G

Variant summary

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

The ENST00000446355.2(ENSG00000237813):​n.112+1731T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 152,276 control chromosomes in the GnomAD database, including 610 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 0.072 (610 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENST00000446355.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

Genes affected

(HGNC:):

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000446355.2	n.112+1731T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10985 AN: 152158 Hom.: 612 Cov.: 32

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.0544

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.0721 AC: 10982 AN: 152274 Hom.: 610 Cov.: 32 AF XY: 0.0774 AC XY: 5761 AN XY: 74448

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.0727

Gnomad4 OTH AF: 0.0534

Alfa AF: 0.0660 Hom.: 41

Bravo AF: 0.0649

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.4
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17138767; hg19: chr7-116137677;