3-8768625-T-C

Variant names:

• chr3-8768625-T-C
• rs237915
• NM_000916.4:c.-238-34A>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.-238-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 158,214 control chromosomes in the GnomAD database, including 4,527 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 0.22 (4251 hom., cov: 31)
  • Exomes 𝑓: 0.29 (276 hom.)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 19 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-238-34A>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.-238-34A>G		intron_variant	Intron 1 of 3	1	NM_000916.4	ENSP00000324270.2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32916 AN: 151848 Hom.: 4253 Cov.: 31

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.292 AC: 1825 AN: 6246 Hom.: 276 Cov.: 0 AF XY: 0.287 AC XY: 907 AN XY: 3160

African (AFR) AF: 0.100 AC: 31 AN: 310

American (AMR) AF: 0.234 AC: 36 AN: 154

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 95 AN: 286

East Asian (EAS) AF: 0.0607 AC: 13 AN: 214

South Asian (SAS) AF: 0.258 AC: 16 AN: 62

European-Finnish (FIN) AF: 0.270 AC: 68 AN: 252

Middle Eastern (MID) AF: 0.333 AC: 6 AN: 18

European-Non Finnish (NFE) AF: 0.318 AC: 1445 AN: 4538

Other (OTH) AF: 0.279 AC: 115 AN: 412

GnomAD4 genome AF: 0.217 AC: 32916 AN: 151968 Hom.: 4251 Cov.: 31 AF XY: 0.214 AC XY: 15912 AN XY: 74256

African (AFR) AF: 0.0853 AC: 3538 AN: 41472

American (AMR) AF: 0.217 AC: 3310 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3468

East Asian (EAS) AF: 0.0503 AC: 258 AN: 5134

South Asian (SAS) AF: 0.267 AC: 1285 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2487 AN: 10548

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.295 AC: 20015 AN: 67942

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.272 Hom.: 3585

Bravo AF: 0.208

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.79
PhyloP100		-0.50
PromoterAI		-0.034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs237915; hg19: chr3-8810311;