rs2301260

Positions:

• chr3-8769543-G-A

Variant summary

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

The NM_000916.4(OXTR):​c.-551C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,326 control chromosomes in the GnomAD database, including 1,291 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 (1291 hom., cov: 34)
  • Exomes 𝑓: 0.075 (0 hom.)
• Consequence: OXTR NM_000916.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXTR	NM_000916.4	c.-551C>T		5_prime_UTR_variant	1/4	ENST00000316793.8
OXTR	NM_001354653.2	c.-471C>T		5_prime_UTR_variant	1/5
OXTR	NM_001354654.2	c.-528C>T		5_prime_UTR_variant	1/4
OXTR	XR_007095681.1	n.71C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXTR	ENST00000316793.8	c.-551C>T		5_prime_UTR_variant	1/4	1	NM_000916.4	P1
OXTR	ENST00000431493.1	c.-528C>T		5_prime_UTR_variant	1/3	4
OXTR	ENST00000474615.1	n.71C>T		non_coding_transcript_exon_variant	1/2	4
CAV3	ENST00000472766.1	n.156-7934G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17611 AN: 152168 Hom.: 1292 Cov.: 34

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0887

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.0750 AC: 3 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0769 AC XY: 2 AN XY: 26

Gnomad4 AFR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0385

GnomAD4 genome AF: 0.116 AC: 17620 AN: 152286 Hom.: 1291 Cov.: 34 AF XY: 0.112 AC XY: 8356 AN XY: 74466

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0858

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0887

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.0362

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.121

Alfa AF: 0.111 Hom.: 151

Bravo AF: 0.123

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.94

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: rs2301260; hg19: chr3-8811229;