chr3-8760797-T-C

Variant names:

• chr3-8760797-T-C
• rs237889
• NM_000916.4:c.922+6469A>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.922+6469A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,064 control chromosomes in the GnomAD database, including 38,623 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 0.70 (38623 hom., cov: 32)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 43 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000916.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXTR	NM_000916.4	MANE Select	c.922+6469A>G		intron	N/A	NP_000907.2
	OXTR	NM_001354653.2		c.922+6469A>G		intron	N/A	NP_001341582.1	B2R9L7
	OXTR	NM_001354654.2		c.922+6469A>G		intron	N/A	NP_001341583.1	P30559

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXTR	ENST00000316793.8	TSL:1 MANE Select	c.922+6469A>G		intron	N/A	ENSP00000324270.2	P30559
	OXTR	ENST00000894689.1		c.922+6469A>G		intron	N/A	ENSP00000564748.1
	OXTR	ENST00000894690.1		c.922+6469A>G		intron	N/A	ENSP00000564749.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106867 AN: 151946 Hom.: 38562 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.704 AC: 106994 AN: 152064 Hom.: 38623 Cov.: 32 AF XY: 0.701 AC XY: 52074 AN XY: 74296

African (AFR) AF: 0.866 AC: 35948 AN: 41496

American (AMR) AF: 0.749 AC: 11447 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2142 AN: 3466

East Asian (EAS) AF: 0.575 AC: 2962 AN: 5154

South Asian (SAS) AF: 0.563 AC: 2710 AN: 4812

European-Finnish (FIN) AF: 0.650 AC: 6862 AN: 10550

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42580 AN: 67976

Other (OTH) AF: 0.693 AC: 1464 AN: 2112

Alfa AF: 0.652 Hom.: 55069

Bravo AF: 0.720

Asia WGS AF: 0.603 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		-0.48
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: rs237889; hg19: chr3-8802483;