chr3-8753808-C-A

Variant names:

• chr3-8753808-C-A
• rs2139184
• NM_000916.4:c.923-584G>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.923-584G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 110,684 control chromosomes in the GnomAD database, including 957 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 0.10 (957 hom., cov: 32)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 10 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.923-584G>T		intron_variant	Intron 3 of 3	ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.923-584G>T		intron_variant	Intron 3 of 3	1	NM_000916.4	ENSP00000324270.2
CAV3	ENST00000472766.1	n.155+19818C>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 11137 AN: 110618 Hom.: 954 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.00801

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.0388

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.0100

Gnomad MID AF: 0.0397

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0816

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 11139 AN: 110684 Hom.: 957 Cov.: 32 AF XY: 0.101 AC XY: 5449 AN XY: 54186

African (AFR) AF: 0.278 AC: 8405 AN: 30184

American (AMR) AF: 0.0616 AC: 679 AN: 11030

Ashkenazi Jewish (ASJ) AF: 0.0388 AC: 94 AN: 2424

East Asian (EAS) AF: 0.156 AC: 734 AN: 4718

South Asian (SAS) AF: 0.0840 AC: 281 AN: 3344

European-Finnish (FIN) AF: 0.0100 AC: 74 AN: 7394

Middle Eastern (MID) AF: 0.0304 AC: 7 AN: 230

European-Non Finnish (NFE) AF: 0.0150 AC: 739 AN: 49222

Other (OTH) AF: 0.0799 AC: 121 AN: 1514

Alfa AF: 0.0259 Hom.: 258

Bravo AF: 0.0813

Asia WGS AF: 0.0760 AC: 264 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.5
DANN	Benign	0.71
PhyloP100		1.3
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: rs2139184; hg19: chr3-8795494;