rs2301260

Variant names:

• chr3-8769543-G-A
• rs2301260
• NM_000916.4:c.-551C>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.-551C>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• Publications: 7 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=-0.73).
• 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 rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-551C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	ENST00000316793.8	NP_000907.2
OXTR	NM_000916.4	c.-551C>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.-551C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1	NM_000916.4	ENSP00000324270.2
OXTR	ENST00000316793.8	c.-551C>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_000916.4	ENSP00000324270.2

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

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0385 AC: 1 AN: 26

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.212 AC: 8826 AN: 41546

American (AMR) AF: 0.0858 AC: 1314 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3472

East Asian (EAS) AF: 0.0887 AC: 459 AN: 5174

South Asian (SAS) AF: 0.0793 AC: 383 AN: 4830

European-Finnish (FIN) AF: 0.0362 AC: 384 AN: 10620

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5535 AN: 68014

Other (OTH) AF: 0.121 AC: 255 AN: 2114

Alfa AF: 0.115 Hom.: 170

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
PhyloP100		0.62
PromoterAI		-0.030	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301260; hg19: chr3-8811229;