rs237911

chr3-8768322-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.-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

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=-0.8).
• 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/exons	MANE	UniProt
OXTR	NM_000916.4	c.-135C>T		5_prime_UTR_variant	3/4	ENST00000316793.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXTR	ENST00000316793.8	c.-135C>T		5_prime_UTR_variant	3/4	1	NM_000916.4	P1
OXTR	ENST00000431493.1	c.-135C>T		5_prime_UTR_variant	3/3	4
OXTR	ENST00000449615.1	c.-135C>T		5_prime_UTR_variant	2/2	2
CAV3	ENST00000472766.1	n.156-9155G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.921

Gnomad4 AMR exome AF: 0.720

Gnomad4 ASJ exome AF: 0.881

Gnomad4 EAS exome AF: 0.753

Gnomad4 SAS exome AF: 0.917

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.853

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

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.854

Alfa AF: 0.846 Hom.: 15571

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

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

Publications

LitVar

Other links and lift over

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