12-49991880-T-C

Position:

• chr12-49991880-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.1714+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,539,136 control chromosomes in the GnomAD database, including 25,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1821 hom., cov: 29)
  • Exomes 𝑓: 0.18 (23647 hom.)
• Consequence: RACGAP1 NM_001319999.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.366

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=-0.83).
• BP6: Variant 12-49991880-T-C is Benign according to our data. Variant chr12-49991880-T-C is described in ClinVar as [Benign]. Clinvar id is 1247109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RACGAP1	NM_001319999.2	c.1714+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.1714+118A>G		intron_variant		1	NM_001319999.2	ENSP00000309871.5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21349 AN: 151952 Hom.: 1821 Cov.: 29

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.181 AC: 251488 AN: 1387068 Hom.: 23647 AF XY: 0.181 AC XY: 124616 AN XY: 688584

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.140 AC: 21356 AN: 152068 Hom.: 1821 Cov.: 29 AF XY: 0.142 AC XY: 10545 AN XY: 74332

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.145

Alfa AF: 0.178 Hom.: 625

Bravo AF: 0.132

Asia WGS AF: 0.115 AC: 400 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.62

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: rs7136233; hg19: chr12-50385663;