chr3-8768017-G-A

Variant names:

• chr3-8768017-G-A
• rs2228485
• NM_000916.4:c.171C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000916.4(OXTR):​c.171C>T​(p.Asn57Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.748 in 1,605,674 control chromosomes in the GnomAD database, including 450,697 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 0.71 (39182 hom., cov: 33)
  • Exomes 𝑓: 0.75 (411515 hom.)
• Consequence: OXTR NM_000916.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98
• Publications: 49 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 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.171C>T	p.Asn57Asn	synonymous	Exon 3 of 4	NP_000907.2
	OXTR	NM_001354653.2		c.171C>T	p.Asn57Asn	synonymous	Exon 4 of 5	NP_001341582.1	B2R9L7
	OXTR	NM_001354654.2		c.171C>T	p.Asn57Asn	synonymous	Exon 3 of 4	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.171C>T	p.Asn57Asn	synonymous	Exon 3 of 4	ENSP00000324270.2	P30559
	OXTR	ENST00000894689.1		c.171C>T	p.Asn57Asn	synonymous	Exon 3 of 4	ENSP00000564748.1
	OXTR	ENST00000894690.1		c.171C>T	p.Asn57Asn	synonymous	Exon 3 of 4	ENSP00000564749.1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108647 AN: 152002 Hom.: 39177 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.715

GnomAD2 exomes AF: 0.734 AC: 170474 AN: 232408 AF XY: 0.746

Gnomad AFR exome AF: 0.637

Gnomad AMR exome AF: 0.591

Gnomad ASJ exome AF: 0.753

Gnomad EAS exome AF: 0.725

Gnomad FIN exome AF: 0.784

Gnomad NFE exome AF: 0.756

Gnomad OTH exome AF: 0.735

GnomAD4 exome AF: 0.751 AC: 1091879 AN: 1453556 Hom.: 411515 Cov.: 64 AF XY: 0.754 AC XY: 544803 AN XY: 722500

African (AFR) AF: 0.633 AC: 20969 AN: 33134

American (AMR) AF: 0.598 AC: 26222 AN: 43818

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 19437 AN: 25960

East Asian (EAS) AF: 0.684 AC: 26829 AN: 39224

South Asian (SAS) AF: 0.823 AC: 69935 AN: 85022

European-Finnish (FIN) AF: 0.777 AC: 40437 AN: 52018

Middle Eastern (MID) AF: 0.789 AC: 4513 AN: 5720

European-Non Finnish (NFE) AF: 0.757 AC: 838853 AN: 1108620

Other (OTH) AF: 0.744 AC: 44684 AN: 60040

GnomAD4 genome AF: 0.715 AC: 108697 AN: 152118 Hom.: 39182 Cov.: 33 AF XY: 0.718 AC XY: 53415 AN XY: 74352

African (AFR) AF: 0.640 AC: 26545 AN: 41506

American (AMR) AF: 0.648 AC: 9907 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2565 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3677 AN: 5140

South Asian (SAS) AF: 0.835 AC: 4032 AN: 4828

European-Finnish (FIN) AF: 0.787 AC: 8342 AN: 10606

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.753 AC: 51203 AN: 67970

Other (OTH) AF: 0.710 AC: 1496 AN: 2106

Alfa AF: 0.737 Hom.: 24021

Bravo AF: 0.699

Asia WGS AF: 0.734 AC: 2555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.2
DANN	Benign	0.96
PhyloP100		5.0
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: rs2228485; hg19: chr3-8809703; COSMIC: COSV57478262; COSMIC: COSV57478262;