3-8769210-C-T

Variant names:

• chr3-8769210-C-T
• rs2301261
• NM_000916.4:c.-239+21G>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.-239+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,472 control chromosomes in the GnomAD database, including 1,404 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 0.12 (1402 hom., cov: 33)
  • Exomes 𝑓: 0.13 (2 hom.)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• Publications: 23 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-239+21G>A		intron_variant	Intron 1 of 3	ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.-239+21G>A		intron_variant	Intron 1 of 3	1	NM_000916.4	ENSP00000324270.2
OXTR	ENST00000431493.1	c.-239+44G>A		intron_variant	Intron 1 of 2	4		ENSP00000414828.1
CAV3	ENST00000472766.1	n.156-8267C>T		intron_variant	Intron 1 of 2	2
OXTR	ENST00000474615.1	n.383+21G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18469 AN: 152188 Hom.: 1404 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.131 AC: 22 AN: 168 Hom.: 2 Cov.: 0 AF XY: 0.123 AC XY: 17 AN XY: 138

African (AFR) AF: 0.125 AC: 1 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.140 AC: 19 AN: 136

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.121 AC: 18477 AN: 152304 Hom.: 1402 Cov.: 33 AF XY: 0.118 AC XY: 8781 AN XY: 74476

African (AFR) AF: 0.217 AC: 9036 AN: 41554

American (AMR) AF: 0.102 AC: 1568 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.0897 AC: 465 AN: 5182

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4824

European-Finnish (FIN) AF: 0.0329 AC: 350 AN: 10626

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0858 AC: 5837 AN: 68030

Other (OTH) AF: 0.134 AC: 283 AN: 2108

Alfa AF: 0.0967 Hom.: 1376

Bravo AF: 0.129

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.8
DANN	Benign	0.77
PhyloP100		-0.70
PromoterAI		-0.097	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2301261; hg19: chr3-8810896;