3-8749653-G-T

Variant names:

• chr3-8749653-G-T
• rs11720238
• ENST00000472766.1:n.155+15663G>T

Variant summary

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

The ENST00000472766.1(CAV3):​n.155+15663G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,168 control chromosomes in the GnomAD database, including 1,316 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 0.13 (1316 hom., cov: 33)
• Consequence: CAV3 ENST00000472766.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	XR_007095681.1	n.1884+3231C>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000472766.1	n.155+15663G>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19212 AN: 152050 Hom.: 1313 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.126 AC: 19234 AN: 152168 Hom.: 1316 Cov.: 33 AF XY: 0.122 AC XY: 9095 AN XY: 74402

African (AFR) AF: 0.171 AC: 7105 AN: 41496

American (AMR) AF: 0.0994 AC: 1519 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0652 AC: 226 AN: 3466

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5184

South Asian (SAS) AF: 0.0280 AC: 135 AN: 4828

European-Finnish (FIN) AF: 0.112 AC: 1189 AN: 10584

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.128 AC: 8728 AN: 68006

Other (OTH) AF: 0.127 AC: 269 AN: 2114

Alfa AF: 0.105 Hom.: 297

Bravo AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs11720238; hg19: chr3-8791339;