chrX-132214186-T-G

Variant names:

• chrX-132214186-T-G
• rs139834013
• NM_001271186.2:c.534A>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001271186.2(RAP2C):​c.534A>C​(p.Thr178Thr) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.17

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]

ACMG classification

Our verdict: Benign. The variant received -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. GnomAdExome4 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 GnomAdExome4. There are 531 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position FAILED quality control check.
• BS2: High Hemizygotes in GnomAd4 at 48 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP2C	NM_001271186.2	c.534A>C	p.Thr178Thr	synonymous_variant	Exon 5 of 6	ENST00000370874.2	NP_001258115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP2C	ENST00000370874.2	c.534A>C	p.Thr178Thr	synonymous_variant	Exon 5 of 6	2	NM_001271186.2	ENSP00000359911.1
RAP2C	ENST00000342983.6	c.534A>C	p.Thr178Thr	synonymous_variant	Exon 3 of 4	1		ENSP00000340274.2
RAP2C	ENST00000620646.4	c.336A>C	p.Thr112Thr	synonymous_variant	Exon 5 of 6	5		ENSP00000484870.1
RAP2C	ENST00000460462.1	n.613A>C		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes AF: 0.000945 AC: 106 AN: 112150 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.00222 AC: 402 AN: 180801 AF XY: 0.00232

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 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.: 12 Cov.: 31 AF XY: 0.00147 AC XY: 531 AN XY: 361266

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 26365

Gnomad4 AMR exome AF: 0.000114 AC: 4 AN: 35099

Gnomad4 ASJ exome AF: 0.00166 AC: 32 AN: 19284

Gnomad4 EAS exome AF: 0.0283 AC: 852 AN: 30156

Gnomad4 SAS exome AF: 0.00223 AC: 120 AN: 53826

Gnomad4 FIN exome AF: 0.00420 AC: 170 AN: 40478

Gnomad4 NFE exome AF: 0.000261 AC: 219 AN: 840221

Gnomad4 Remaining exome AF: 0.00174 AC: 80 AN: 46001

GnomAD4 genome AF: 0.000927 AC: 104 AN: 112206 Hom.: 0 Cov.: 23 AF XY: 0.00140 AC XY: 48 AN XY: 34368

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.000377 AC: 0.000377216 AN: 0.000377216

Gnomad4 ASJ AF: 0.00227 AC: 0.00226843 AN: 0.00226843

Gnomad4 EAS AF: 0.0160 AC: 0.0159753 AN: 0.0159753

Gnomad4 SAS AF: 0.00110 AC: 0.00110416 AN: 0.00110416

Gnomad4 FIN AF: 0.00343 AC: 0.00343306 AN: 0.00343306

Gnomad4 NFE AF: 0.000244 AC: 0.000244301 AN: 0.000244301

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000804 Hom.: 12

Bravo AF: 0.000979

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.76
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

Publications

LitVar

Other links and lift over

dbSNP: rs139834013; hg19: chrX-131348214;