rs237913

Positions:

• chr3-8768364-C-A
• chr3-8768364-C-G
• chr3-8768364-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.-142-35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,033,158 control chromosomes in the GnomAD database, including 39,152 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 0.21 (4045 hom., cov: 32)
  • Exomes 𝑓: 0.28 (35107 hom.)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-142-35G>T		intron_variant		ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.-142-35G>T		intron_variant		1	NM_000916.4	ENSP00000324270	P1
OXTR	ENST00000431493.1	c.-142-35G>T		intron_variant		4		ENSP00000414828
OXTR	ENST00000449615.1	c.-142-35G>T		intron_variant		2		ENSP00000389587
CAV3	ENST00000472766.1	n.156-9113C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32644 AN: 152020 Hom.: 4045 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0482

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.275 AC: 242349 AN: 881022 Hom.: 35107 Cov.: 12 AF XY: 0.276 AC XY: 115939 AN XY: 420142

Gnomad4 AFR exome AF: 0.0939

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.215 AC: 32651 AN: 152136 Hom.: 4045 Cov.: 32 AF XY: 0.212 AC XY: 15764 AN XY: 74382

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0480

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.226

Alfa AF: 0.134 Hom.: 280

Bravo AF: 0.205

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.64

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: rs237913; hg19: chr3-8810050;