3-8752859-G-T

Variant names:

• chr3-8752859-G-T
• rs1042778
• NM_000916.4:c.*118C>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.*118C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,124,216 control chromosomes in the GnomAD database, including 89,518 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 0.45 (16610 hom., cov: 31)
  • Exomes 𝑓: 0.38 (72908 hom.)
• Consequence: OXTR NM_000916.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 134 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.*118C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000316793.8	NP_000907.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8	c.*118C>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_000916.4	ENSP00000324270.2
CAV3	ENST00000472766.1	n.155+18869G>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68111 AN: 151594 Hom.: 16568 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.379 AC: 368547 AN: 972504 Hom.: 72908 Cov.: 13 AF XY: 0.379 AC XY: 182571 AN XY: 481984

African (AFR) AF: 0.642 AC: 14310 AN: 22296

American (AMR) AF: 0.447 AC: 8964 AN: 20048

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 6032 AN: 17008

East Asian (EAS) AF: 0.0960 AC: 3208 AN: 33414

South Asian (SAS) AF: 0.366 AC: 20644 AN: 56438

European-Finnish (FIN) AF: 0.376 AC: 11527 AN: 30648

Middle Eastern (MID) AF: 0.342 AC: 1048 AN: 3068

European-Non Finnish (NFE) AF: 0.384 AC: 286426 AN: 746354

Other (OTH) AF: 0.379 AC: 16388 AN: 43230

GnomAD4 genome AF: 0.450 AC: 68211 AN: 151712 Hom.: 16610 Cov.: 31 AF XY: 0.443 AC XY: 32855 AN XY: 74140

African (AFR) AF: 0.637 AC: 26299 AN: 41276

American (AMR) AF: 0.437 AC: 6675 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3468

East Asian (EAS) AF: 0.0866 AC: 446 AN: 5148

South Asian (SAS) AF: 0.353 AC: 1692 AN: 4798

European-Finnish (FIN) AF: 0.373 AC: 3928 AN: 10534

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.391 AC: 26540 AN: 67930

Other (OTH) AF: 0.430 AC: 900 AN: 2092

Alfa AF: 0.399 Hom.: 26143

Bravo AF: 0.464

Asia WGS AF: 0.255 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.054
DANN	Benign	0.61
PhyloP100		-2.1
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: rs1042778; hg19: chr3-8794545; COSMIC: COSV57481700;