rs6770632

Positions:

• chr3-8752038-C-A

Variant summary

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

The ENST00000316793.8(OXTR):​c.*939G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,066 control chromosomes in the GnomAD database, including 7,900 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 0.30 (7900 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OXTR ENST00000316793.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXTR	NM_000916.4	c.*939G>T		3_prime_UTR_variant	4/4	ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.*939G>T		3_prime_UTR_variant	4/4	1	NM_000916.4	ENSP00000324270	P1
CAV3	ENST00000472766.1	n.155+18048C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45036 AN: 151948 Hom.: 7879 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.283

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.297 AC: 45104 AN: 152066 Hom.: 7900 Cov.: 33 AF XY: 0.290 AC XY: 21554 AN XY: 74324

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.282

Alfa AF: 0.265 Hom.: 2060

Bravo AF: 0.300

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6770632; hg19: chr3-8793724;