Variant X-132214186-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001271186.2(RAP2C):c.534A>C(p.Thr178=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,207,758 control chromosomes in the GnomAD database, including 12 homozygotes. There are 579 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., 48 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 12 hom. 531 hem. )

Consequence

RAP2C
NM_001271186.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

RAP2C (HGNC:21165): (RAP2C, member of RAS oncogene family) The protein encoded by this gene is a member of the Ras-related protein subfamily of the Ras GTPase superfamily. Members of this family are small GTPases that act as molecular switches to regulate cellular proliferation, differentiation, and apoptosis. This protein has been reported to activate in vitro transcriptional activity of the serum response element. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

RAP2C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-132214186-T-G is Benign according to our data. Variant chrX-132214186-T-G is described in ClinVar as [Benign]. Clinvar id is 789464.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00135 (1481/1095552) while in subpopulation EAS AF= 0.0283 (852/30156). AF 95% confidence interval is 0.0267. There are 12 homozygotes in gnomad4_exome. There are 531 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 48 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP2C	NM_001271186.2 linkuse as main transcript	c.534A>C	p.Thr178=	synonymous_variant	5/6	ENST00000370874.2	NP_001258115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RAP2C	ENST00000370874.2 linkuse as main transcript	c.534A>C	p.Thr178=	synonymous_variant	5/6	2	NM_001271186.2	ENSP00000359911	P1
RAP2C	ENST00000342983.6 linkuse as main transcript	c.534A>C	p.Thr178=	synonymous_variant	3/4	1		ENSP00000340274	P1
RAP2C	ENST00000620646.4 linkuse as main transcript	c.336A>C	p.Thr112=	synonymous_variant	5/6	5		ENSP00000484870
RAP2C	ENST00000460462.1 linkuse as main transcript	n.613A>C		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.000945

AC:

106

AN:

112150

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

AN XY:

34302

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000378

Gnomad ASJ

AF:

0.00227

Gnomad EAS

AF:

0.0159

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.00343

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000263

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00222

AC:

402

AN:

180801

Hom.:

AF XY:

0.00232

AC XY:

152

AN XY:

65567

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00234

Gnomad EAS exome

AF:

0.0165

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00360

Gnomad NFE exome

AF:

0.000646

Gnomad OTH exome

AF:

0.00269

GnomAD4 exome

AF:

0.00135

AC:

1481

AN:

1095552

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

531

AN XY:

361266

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00166

Gnomad4 EAS exome

AF:

0.0283

Gnomad4 SAS exome

AF:

0.00223

Gnomad4 FIN exome

AF:

0.00420

Gnomad4 NFE exome

AF:

0.000261

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.000927

AC:

104

AN:

112206

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

AN XY:

34368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000377

Gnomad4 ASJ

AF:

0.00227

Gnomad4 EAS

AF:

0.0160

Gnomad4 SAS

AF:

0.00110

Gnomad4 FIN

AF:

0.00343

Gnomad4 NFE

AF:

0.000244

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.000979

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over