NM_000916.4:c.-142-35G>T

Variant names:

• chr3-8768364-C-A
• rs237913
• NM_000916.4:c.-142-35G>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.-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
• 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=-0.83).
• 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 rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-142-35G>T		intron_variant	Intron 2 of 3	ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.-142-35G>T		intron_variant	Intron 2 of 3	1	NM_000916.4	ENSP00000324270.2

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

African (AFR) AF: 0.0939 AC: 1727 AN: 18390

American (AMR) AF: 0.165 AC: 1175 AN: 7136

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 3498 AN: 11816

East Asian (EAS) AF: 0.0424 AC: 972 AN: 22912

South Asian (SAS) AF: 0.280 AC: 4263 AN: 15212

European-Finnish (FIN) AF: 0.241 AC: 4900 AN: 20362

Middle Eastern (MID) AF: 0.329 AC: 812 AN: 2468

European-Non Finnish (NFE) AF: 0.289 AC: 215456 AN: 746798

Other (OTH) AF: 0.266 AC: 9546 AN: 35928

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

African (AFR) AF: 0.103 AC: 4286 AN: 41544

American (AMR) AF: 0.188 AC: 2873 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3466

East Asian (EAS) AF: 0.0480 AC: 248 AN: 5170

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2438 AN: 10586

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19542 AN: 67932

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.245 Hom.: 7479

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
PhyloP100		-3.5
PromoterAI		0.028	Neutral
Mutation Taster		=98/2	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: rs237913; hg19: chr3-8810050;