Variant 12-49990686-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001319999.2(RACGAP1):c.1821T>C(p.Pro607Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,605,894 control chromosomes in the GnomAD database, including 2,467 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 1285 hom., cov: 31)

Exomes 𝑓: 0.0072 ( 1182 hom. )

Consequence

RACGAP1
NM_001319999.2 splice_region, synonymous

Scores

Splicing: ADA: 0.0001187

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.757

Variant links:

Genes affected

RACGAP1 (HGNC:9804): (Rac GTPase activating protein 1) This gene encodes a GTPase-activating protein (GAP) that is a compoment of the centralspindlin complex. This protein binds activated forms of Rho GTPases and stimulates GTP hydrolysis, which results in negative regulation of Rho-mediated signals. This protein plays a regulatory role in cytokinesis, cell growth, and differentiation. Alternatively spliced transcript variants have been found for this gene. There is a pseudogene for this gene on chromosome 12. [provided by RefSeq, Feb 2016]

RACGAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 12-49990686-A-G is Benign according to our data. Variant chr12-49990686-A-G is described in ClinVar as [Benign]. Clinvar id is 1232694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.757 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RACGAP1	NM_001319999.2 linkuse as main transcript	c.1821T>C	p.Pro607Pro	splice_region_variant, synonymous_variant	16/17	ENST00000312377.10	NP_001306928.1	Q9H0H5A0A024R136

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RACGAP1	ENST00000312377.10 linkuse as main transcript	c.1821T>C	p.Pro607Pro	splice_region_variant, synonymous_variant	16/17	1	NM_001319999.2	ENSP00000309871.5		Q9H0H5

Frequencies

GnomAD3 genomes

AF:

0.0705

AC:

10717

AN:

152044

Hom.:

1286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0289

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0511

GnomAD3 exomes

AF:

0.0187

AC:

4691

AN:

251094

Hom.:

547

AF XY:

0.0131

AC XY:

1773

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000423

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00717

AC:

10417

AN:

1453732

Hom.:

1182

Cov.:

AF XY:

0.00604

AC XY:

4375

AN XY:

723872

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.000690

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000314

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.0150

GnomAD4 genome

AF:

0.0706

AC:

10742

AN:

152162

Hom.:

1285

Cov.:

AF XY:

0.0675

AC XY:

5024

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.0288

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0506

Alfa

AF:

0.0304

Hom.:

268

Bravo

AF:

0.0814

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.010

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