rs3831817

Variant names:

• chr3-8766742-G-GC
• rs3831817
• NM_000916.4:c.922+523dupG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000916.4(OXTR):​c.922+523dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30485 hom., cov: 0)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.922+523dupG		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.922+523_922+524insG		intron_variant	Intron 3 of 3	1	NM_000916.4	ENSP00000324270.2
CAV3	ENST00000472766.1	n.156-10735_156-10734insC		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94796 AN: 151496 Hom.: 30452 Cov.: 0

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.626 AC: 94885 AN: 151612 Hom.: 30485 Cov.: 0 AF XY: 0.615 AC XY: 45545 AN XY: 74110

African (AFR) AF: 0.762 AC: 31454 AN: 41284

American (AMR) AF: 0.628 AC: 9584 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2040 AN: 3466

East Asian (EAS) AF: 0.309 AC: 1590 AN: 5150

South Asian (SAS) AF: 0.555 AC: 2673 AN: 4812

European-Finnish (FIN) AF: 0.441 AC: 4636 AN: 10520

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40846 AN: 67802

Other (OTH) AF: 0.619 AC: 1308 AN: 2112

Alfa AF: 0.614 Hom.: 3105

Bravo AF: 0.644

Asia WGS AF: 0.479 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0060
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: rs3831817; hg19: chr3-8808428;