rs7632287

Variant names:

• chr3-8749760-G-A
• rs7632287
• ENST00000472766.1:n.155+15770G>A

Variant summary

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

The ENST00000472766.1(CAV3):​n.155+15770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,142 control chromosomes in the GnomAD database, including 9,045 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 0.31 (9045 hom., cov: 33)
• Consequence: CAV3 ENST00000472766.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 71 publications found

Genes affected

CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]

OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	XR_007095681.1	n.1884+3124C>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000472766.1	n.155+15770G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46912 AN: 152024 Hom.: 9023 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.309 AC: 46987 AN: 152142 Hom.: 9045 Cov.: 33 AF XY: 0.302 AC XY: 22465 AN XY: 74378

African (AFR) AF: 0.544 AC: 22551 AN: 41480

American (AMR) AF: 0.202 AC: 3084 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5172

South Asian (SAS) AF: 0.0680 AC: 328 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2919 AN: 10592

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16626 AN: 68000

Other (OTH) AF: 0.283 AC: 599 AN: 2114

Alfa AF: 0.257 Hom.: 4698

Bravo AF: 0.315

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.74
PhyloP100		0.073

Splicing

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

Other links and lift over

dbSNP: rs7632287; hg19: chr3-8791446;