NM_000916.4:c.-238-131C>G

Variant names:

• chr3-8768722-G-C
• rs4564970
• NM_000916.4:c.-238-131C>G

Variant summary

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

The NM_000916.4(OXTR):​c.-238-131C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,432 control chromosomes in the GnomAD database, including 1,803 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 0.13 (1800 hom., cov: 32)
  • Exomes 𝑓: 0.089 (3 hom.)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 24 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-238-131C>G		intron_variant	Intron 1 of 3	ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.-238-131C>G		intron_variant	Intron 1 of 3	1	NM_000916.4	ENSP00000324270.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20327 AN: 151944 Hom.: 1799 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0892 AC: 33 AN: 370 Hom.: 3 Cov.: 0 AF XY: 0.0867 AC XY: 17 AN XY: 196

African (AFR) AF: 0.200 AC: 4 AN: 20

American (AMR) AF: 0.167 AC: 1 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 2 AN: 10

East Asian (EAS) AF: 0.125 AC: 1 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0714 AC: 21 AN: 294

Other (OTH) AF: 0.100 AC: 2 AN: 20

GnomAD4 genome AF: 0.134 AC: 20355 AN: 152062 Hom.: 1800 Cov.: 32 AF XY: 0.130 AC XY: 9637 AN XY: 74328

African (AFR) AF: 0.259 AC: 10717 AN: 41424

American (AMR) AF: 0.107 AC: 1635 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3472

East Asian (EAS) AF: 0.0760 AC: 391 AN: 5148

South Asian (SAS) AF: 0.0960 AC: 463 AN: 4824

European-Finnish (FIN) AF: 0.0332 AC: 352 AN: 10610

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0875 AC: 5951 AN: 67978

Other (OTH) AF: 0.141 AC: 299 AN: 2114

Alfa AF: 0.0351 Hom.: 30

Bravo AF: 0.143

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.2
DANN	Benign	0.77
PhyloP100		-0.38
PromoterAI		0.054	Neutral
Mutation Taster		=100/0	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: rs4564970; hg19: chr3-8810408;