3-8767498-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000916.4(OXTR):c.690C>T(p.Asn230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,610,256 control chromosomes in the GnomAD database, including 90,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7483 hom., cov: 33)
  • Exomes 𝑓: 0.33 (82748 hom.)
• Consequence: OXTR NM_000916.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.896

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-8767498-G-A is Benign according to our data. Variant chr3-8767498-G-A is described in ClinVar as [Benign]. Clinvar id is 3058957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.896 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXTR	NM_000916.4	c.690C>T	p.Asn230=	synonymous_variant	3/4	ENST00000316793.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXTR	ENST00000316793.8	c.690C>T	p.Asn230=	synonymous_variant	3/4	1	NM_000916.4	P1
CAV3	ENST00000472766.1	n.156-9979G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46919 AN: 152036 Hom.: 7481 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.288 AC: 68958 AN: 239468 Hom.: 10997 AF XY: 0.295 AC XY: 38457 AN XY: 130350

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.0426

Gnomad SAS exome AF: 0.301

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.330 AC: 481841 AN: 1458108 Hom.: 82748 Cov.: 52 AF XY: 0.331 AC XY: 239790 AN XY: 725138

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.0426

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.309 AC: 46941 AN: 152148 Hom.: 7483 Cov.: 33 AF XY: 0.302 AC XY: 22476 AN XY: 74370

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.0400

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.310

Alfa AF: 0.330 Hom.: 5343

Bravo AF: 0.308

Asia WGS AF: 0.170 AC: 589 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

OXTR-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.8
Dann	Benign	0.94

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: rs237902; hg19: chr3-8809184; COSMIC: COSV57480268; COSMIC: COSV57480268;