12-49990566-T-C

Position:

• chr12-49990566-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001319999.2(RACGAP1):​c.1823+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 892,430 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.042 (419 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (296 hom.)
• Consequence: RACGAP1 NM_001319999.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.549

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-49990566-T-C is Benign according to our data. Variant chr12-49990566-T-C is described in ClinVar as [Benign]. Clinvar id is 1229294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RACGAP1	NM_001319999.2	c.1823+118A>G		intron_variant		ENST00000312377.10	NP_001306928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RACGAP1	ENST00000312377.10	c.1823+118A>G		intron_variant		1	NM_001319999.2	ENSP00000309871.5

Frequencies

GnomAD3 genomes AF: 0.0418 AC: 6358 AN: 152152 Hom.: 416 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0240

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.00797 AC: 5898 AN: 740160 Hom.: 296 AF XY: 0.00752 AC XY: 2877 AN XY: 382610

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0495

Gnomad4 SAS exome AF: 0.0121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000306

Gnomad4 OTH exome AF: 0.0132

GnomAD4 genome AF: 0.0420 AC: 6396 AN: 152270 Hom.: 419 Cov.: 32 AF XY: 0.0406 AC XY: 3021 AN XY: 74478

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.00717 Hom.: 115

Bravo AF: 0.0477

Asia WGS AF: 0.0410 AC: 142 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.54

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: rs2292721; hg19: chr12-50384349;