rs237911

Variant names:

• chr3-8768322-G-A
• rs237911
• NM_000916.4:c.-135C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000916.4(OXTR):​c.-135C>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 0.846 in 1,202,400 control chromosomes in the GnomAD database, including 430,865 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 0.85 (55544 hom., cov: 32)
  • Exomes 𝑓: 0.84 (375321 hom.)
• Consequence: OXTR NM_000916.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 23 publications found

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]

CAV3 Gene-Disease associations (from GenCC):

• caveolinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1C

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• long QT syndrome 9

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• rippling muscle disease 2

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• distal myopathy, Tateyama type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• inherited rippling muscle disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Brugada syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
• hypertrophic cardiomyopathy 1

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• long QT syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-135C>T		5_prime_UTR_variant	Exon 3 of 4	ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.-135C>T		5_prime_UTR_variant	Exon 3 of 4	1	NM_000916.4	ENSP00000324270.2

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129669 AN: 152016 Hom.: 55520 Cov.: 32

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.858

GnomAD4 exome AF: 0.845 AC: 887432 AN: 1050270 Hom.: 375321 Cov.: 21 AF XY: 0.845 AC XY: 418939 AN XY: 495990

African (AFR) AF: 0.921 AC: 19949 AN: 21664

American (AMR) AF: 0.720 AC: 5378 AN: 7468

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 11435 AN: 12974

East Asian (EAS) AF: 0.753 AC: 18061 AN: 23986

South Asian (SAS) AF: 0.917 AC: 17102 AN: 18660

European-Finnish (FIN) AF: 0.816 AC: 16947 AN: 20772

Middle Eastern (MID) AF: 0.907 AC: 2515 AN: 2772

European-Non Finnish (NFE) AF: 0.845 AC: 760454 AN: 900264

Other (OTH) AF: 0.853 AC: 35591 AN: 41710

GnomAD4 genome AF: 0.853 AC: 129741 AN: 152130 Hom.: 55544 Cov.: 32 AF XY: 0.853 AC XY: 63418 AN XY: 74386

African (AFR) AF: 0.914 AC: 37939 AN: 41524

American (AMR) AF: 0.761 AC: 11640 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3472

East Asian (EAS) AF: 0.793 AC: 4064 AN: 5124

South Asian (SAS) AF: 0.917 AC: 4427 AN: 4826

European-Finnish (FIN) AF: 0.822 AC: 8700 AN: 10590

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57124 AN: 67978

Other (OTH) AF: 0.854 AC: 1806 AN: 2114

Alfa AF: 0.845 Hom.: 17176

Bravo AF: 0.848

Asia WGS AF: 0.828 AC: 2882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.91
PhyloP100		-1.7
PromoterAI		0.029	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs237911; hg19: chr3-8810008; COSMIC: COSV57481180; COSMIC: COSV57481180;