12-49992505-G-GA

Position:

• chr12-49992505-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001319999.2(RACGAP1):​c.1445+44dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00959 in 1,592,748 control chromosomes in the GnomAD database, including 877 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.042 (416 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (461 hom.)
• Consequence: RACGAP1 NM_001319999.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0390

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 -10 ACMG points.

• BP6: Variant 12-49992505-G-GA is Benign according to our data. Variant chr12-49992505-G-GA is described in ClinVar as [Benign]. Clinvar id is 1295130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RACGAP1	NM_001319999.2	c.1445+44dupT		intron_variant		ENST00000312377.10	NP_001306928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RACGAP1	ENST00000312377.10	c.1445+44dupT		intron_variant		1	NM_001319999.2	ENSP00000309871.5

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6339 AN: 151972 Hom.: 413 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0272

GnomAD3 exomes AF: 0.0139 AC: 3341 AN: 240152 Hom.: 202 AF XY: 0.0109 AC XY: 1413 AN XY: 129936

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.00659

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0151

Gnomad SAS exome AF: 0.0137

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00924

GnomAD4 exome AF: 0.00618 AC: 8899 AN: 1440658 Hom.: 461 Cov.: 30 AF XY: 0.00588 AC XY: 4213 AN XY: 716414

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.00838

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0470

Gnomad4 SAS exome AF: 0.0119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0419 AC: 6375 AN: 152090 Hom.: 416 Cov.: 32 AF XY: 0.0405 AC XY: 3009 AN XY: 74364

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0178 Hom.: 31

Bravo AF: 0.0474

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs3215252; hg19: chr12-50386288;