rs17138765

Positions:

• chr7-116497472-G-A

Variant summary

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

The ENST00000446355.2(ENSG00000237813):​n.112+1882C>T 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 0.102 in 152,212 control chromosomes in the GnomAD database, including 973 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 0.10 (973 hom., cov: 32)
• Consequence: ENST00000446355.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000446355.2	n.112+1882C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15519 AN: 152096 Hom.: 967 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15547 AN: 152212 Hom.: 973 Cov.: 32 AF XY: 0.0980 AC XY: 7295 AN XY: 74414

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0699

Gnomad4 ASJ AF: 0.0899

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0845

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0889 Hom.: 126

Bravo AF: 0.108

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17138765; hg19: chr7-116137526;