rs2228485

chr3-8768017-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000916.4(OXTR):c.171C>T(p.Asn57=) variant causes a synonymous change. The variant allele was found at a frequency of 0.748 in 1,605,674 control chromosomes in the GnomAD database, including 450,697 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 0.71 (39182 hom., cov: 33)
  • Exomes 𝑓: 0.75 (411515 hom.)
• Consequence: OXTR NM_000916.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXTR	NM_000916.4	c.171C>T	p.Asn57=	synonymous_variant	3/4	ENST00000316793.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXTR	ENST00000316793.8	c.171C>T	p.Asn57=	synonymous_variant	3/4	1	NM_000916.4	P1
OXTR	ENST00000449615.1	c.171C>T	p.Asn57=	synonymous_variant	2/2	2
CAV3	ENST00000472766.1	n.156-9460G>A		intron_variant, non_coding_transcript_variant		2
OXTR	ENST00000431493.1			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108647 AN: 152002 Hom.: 39177 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.715

GnomAD3 exomes AF: 0.734 AC: 170474 AN: 232408 Hom.: 63102 AF XY: 0.746 AC XY: 94682 AN XY: 126864

Gnomad AFR exome AF: 0.637

Gnomad AMR exome AF: 0.591

Gnomad ASJ exome AF: 0.753

Gnomad EAS exome AF: 0.725

Gnomad SAS exome AF: 0.827

Gnomad FIN exome AF: 0.784

Gnomad NFE exome AF: 0.756

Gnomad OTH exome AF: 0.735

GnomAD4 exome AF: 0.751 AC: 1091879 AN: 1453556 Hom.: 411515 Cov.: 64 AF XY: 0.754 AC XY: 544803 AN XY: 722500

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.749

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.823

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.757

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.715 AC: 108697 AN: 152118 Hom.: 39182 Cov.: 33 AF XY: 0.718 AC XY: 53415 AN XY: 74352

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.710

Alfa AF: 0.740 Hom.: 17266

Bravo AF: 0.699

Asia WGS AF: 0.734 AC: 2555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	7.2
Dann	Benign	0.96

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: rs2228485; hg19: chr3-8809703; COSMIC: COSV57478262; COSMIC: COSV57478262;