3-8768722-G-C

Variant names:

• chr3-8768722-G-C
• rs4564970
• NM_000916.4:c.-238-131C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354656.3(OXTR):​c.-273C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,432 control chromosomes in the GnomAD database, including 1,803 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 0.13 (1800 hom., cov: 32)
  • Exomes 𝑓: 0.089 (3 hom.)
• Consequence: OXTR NM_001354656.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXTR	NM_000916.4	c.-238-131C>G		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.-238-131C>G		intron_variant	Intron 1 of 3	1	NM_000916.4	ENSP00000324270.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20327 AN: 151944 Hom.: 1799 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0892 AC: 33 AN: 370 Hom.: 3 Cov.: 0 AF XY: 0.0867 AC XY: 17 AN XY: 196

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.134 AC: 20355 AN: 152062 Hom.: 1800 Cov.: 32 AF XY: 0.130 AC XY: 9637 AN XY: 74328

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0760

Gnomad4 SAS AF: 0.0960

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.0875

Gnomad4 OTH AF: 0.141

Alfa AF: 0.0351 Hom.: 30

Bravo AF: 0.143

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.2
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs4564970; hg19: chr3-8810408;