3-8755399-C-T

Variant names:

• chr3-8755399-C-T
• rs2268490
• NM_000916.4:c.923-2175G>A

Variant summary

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

The NM_000916.4(OXTR):​c.923-2175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,222 control chromosomes in the GnomAD database, including 3,019 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 0.18 (3019 hom., cov: 34)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 40 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 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.923-2175G>A		intron	N/A	NP_000907.2
	OXTR	NM_001354653.2		c.923-2175G>A		intron	N/A	NP_001341582.1	B2R9L7
	OXTR	NM_001354654.2		c.923-2175G>A		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.923-2175G>A		intron	N/A	ENSP00000324270.2	P30559
	OXTR	ENST00000894689.1		c.923-2175G>A		intron	N/A	ENSP00000564748.1
	OXTR	ENST00000894690.1		c.923-2175G>A		intron	N/A	ENSP00000564749.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27863 AN: 152104 Hom.: 3021 Cov.: 34

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.183 AC: 27891 AN: 152222 Hom.: 3019 Cov.: 34 AF XY: 0.185 AC XY: 13781 AN XY: 74434

African (AFR) AF: 0.225 AC: 9345 AN: 41526

American (AMR) AF: 0.244 AC: 3731 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3468

East Asian (EAS) AF: 0.494 AC: 2557 AN: 5180

South Asian (SAS) AF: 0.157 AC: 758 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1130 AN: 10582

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9060 AN: 68024

Other (OTH) AF: 0.203 AC: 428 AN: 2112

Alfa AF: 0.157 Hom.: 3528

Bravo AF: 0.199

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.99
DANN	Benign	0.27
PhyloP100		-0.30
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: rs2268490; hg19: chr3-8797085;