rs237884

Positions:

• chr3-8751899-G-A
• chr3-8751899-G-C
• chr3-8751899-G-T

Variant summary

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

The NM_000916.4(OXTR):​c.*1078C>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 0.677 in 152,086 control chromosomes in the GnomAD database, including 36,661 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 0.68 (36661 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: OXTR NM_000916.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXTR	NM_000916.4	c.*1078C>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.*1078C>T		3_prime_UTR_variant	4/4	1	NM_000916.4	ENSP00000324270	P1
CAV3	ENST00000472766.1	n.155+17909G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102932 AN: 151968 Hom.: 36661 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.677 AC: 102959 AN: 152086 Hom.: 36661 Cov.: 32 AF XY: 0.684 AC XY: 50816 AN XY: 74338

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.697

Alfa AF: 0.737 Hom.: 39721

Bravo AF: 0.671

Asia WGS AF: 0.889 AC: 3089 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.68

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: rs237884; hg19: chr3-8793585;