chr3-8767498-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000916.4(OXTR):c.690C>T(p.Asn230Asn) 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 (no stars).

Frequency

Genomes: 𝑓 0.31 ( 7483 hom., cov: 33)

Exomes 𝑓: 0.33 ( 82748 hom. )

Consequence

OXTR
NM_000916.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.896

Publications

52 publications found

Variant links:

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]

OXTR links:

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

CAV3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
OXTR	NM_000916.4 link	c.690C>T	p.Asn230Asn	synonymous_variant	Exon 3 of 4	ENST00000316793.8	NP_000907.2	P30559B2R9L7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXTR	ENST00000316793.8 link	c.690C>T	p.Asn230Asn	synonymous_variant	Exon 3 of 4	1	NM_000916.4	ENSP00000324270.2		P30559
CAV3	ENST00000472766.1 link	n.156-9979G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46919

AN:

152036

Hom.:

7481

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.288

AC:

68958

AN:

239468

AF XY:

0.295

show subpopulations

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 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.:

AF XY:

0.331

AC XY:

239790

AN XY:

725138

show subpopulations

African (AFR)

AF:

0.309

AC:

10322

AN:

33378

American (AMR)

AF:

0.218

AC:

9642

AN:

44304

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8654

AN:

26068

East Asian (EAS)

AF:

0.0426

AC:

1687

AN:

39584

South Asian (SAS)

AF:

0.307

AC:

26421

AN:

86012

European-Finnish (FIN)

AF:

0.275

AC:

14448

AN:

52510

Middle Eastern (MID)

AF:

0.365

AC:

2102

AN:

5762

European-Non Finnish (NFE)

AF:

0.350

AC:

388839

AN:

1110264

Other (OTH)

AF:

0.328

AC:

19726

AN:

60226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

19650

39299

58949

78598

98248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.309

AC:

46941

AN:

152148

Hom.:

7483

Cov.:

AF XY:

0.302

AC XY:

22476

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.307

AC:

12740

AN:

41508

American (AMR)

AF:

0.263

AC:

4027

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

1127

AN:

3470

East Asian (EAS)

AF:

0.0400

AC:

207

AN:

5170

South Asian (SAS)

AF:

0.298

AC:

1440

AN:

4826

European-Finnish (FIN)

AF:

0.259

AC:

2745

AN:

10582

Middle Eastern (MID)

AF:

0.338

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.345

AC:

23479

AN:

67980

Other (OTH)

AF:

0.310

AC:

654

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1692

3384

5075

6767

8459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.325

Hom.:

7244

Bravo

AF:

0.308

Asia WGS

AF:

0.170

AC:

589

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OXTR-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.94

PhyloP100

0.90

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr3-8767498-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over