rs2301261

Positions:

• chr3-8769210-C-T

Variant summary

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

The NM_000916.4(OXTR):​c.-239+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,472 control chromosomes in the GnomAD database, including 1,404 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 0.12 (1402 hom., cov: 33)
  • Exomes 𝑓: 0.13 (2 hom.)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-239+21G>A		intron_variant		ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.-239+21G>A		intron_variant		1	NM_000916.4	ENSP00000324270	P1
OXTR	ENST00000431493.1	c.-239+44G>A		intron_variant		4		ENSP00000414828
CAV3	ENST00000472766.1	n.156-8267C>T		intron_variant, non_coding_transcript_variant		2
OXTR	ENST00000474615.1	n.383+21G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18469 AN: 152188 Hom.: 1404 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.131 AC: 22 AN: 168 Hom.: 2 Cov.: 0 AF XY: 0.123 AC XY: 17 AN XY: 138

Gnomad4 AFR exome AF: 0.125

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.121 AC: 18477 AN: 152304 Hom.: 1402 Cov.: 33 AF XY: 0.118 AC XY: 8781 AN XY: 74476

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0897

Gnomad4 SAS AF: 0.0817

Gnomad4 FIN AF: 0.0329

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0921 Hom.: 940

Bravo AF: 0.129

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.8
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2301261; hg19: chr3-8810896;