12-49992232-C-T

Position:

• chr12-49992232-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001319999.2(RACGAP1):​c.1578+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 1,613,696 control chromosomes in the GnomAD database, including 647,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (47431 hom., cov: 30)
  • Exomes 𝑓: 0.90 (600417 hom.)
• Consequence: RACGAP1 NM_001319999.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.220

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-49992232-C-T is Benign according to our data. Variant chr12-49992232-C-T is described in ClinVar as [Benign]. Clinvar id is 1262134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RACGAP1	NM_001319999.2	c.1578+13G>A		intron_variant		ENST00000312377.10	NP_001306928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RACGAP1	ENST00000312377.10	c.1578+13G>A		intron_variant		1	NM_001319999.2	ENSP00000309871.5

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112099 AN: 152024 Hom.: 47426 Cov.: 30

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.777

GnomAD3 exomes AF: 0.858 AC: 215678 AN: 251290 Hom.: 95992 AF XY: 0.869 AC XY: 118030 AN XY: 135802

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.822

Gnomad ASJ exome AF: 0.927

Gnomad EAS exome AF: 0.932

Gnomad SAS exome AF: 0.827

Gnomad FIN exome AF: 0.961

Gnomad NFE exome AF: 0.925

Gnomad OTH exome AF: 0.878

GnomAD4 exome AF: 0.900 AC: 1315430 AN: 1461554 Hom.: 600417 Cov.: 70 AF XY: 0.900 AC XY: 654530 AN XY: 727054

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.927

Gnomad4 EAS exome AF: 0.892

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.960

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.869

GnomAD4 genome AF: 0.737 AC: 112127 AN: 152142 Hom.: 47431 Cov.: 30 AF XY: 0.745 AC XY: 55375 AN XY: 74374

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.776

Alfa AF: 0.888 Hom.: 56525

Bravo AF: 0.704

Asia WGS AF: 0.822 AC: 2856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.44

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: rs296737; hg19: chr12-50386015;