12-49978243-C-T

Position:

• chr12-49978243-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000548961.5(RACGAP1):​c.245-1184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,154 control chromosomes in the GnomAD database, including 1,035 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.096 (1035 hom., cov: 32)
• Consequence: RACGAP1 ENST00000548961.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RACGAP1	ENST00000548961.5	c.245-1184G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14557 AN: 152036 Hom.: 1041 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0903

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0957 AC: 14558 AN: 152154 Hom.: 1035 Cov.: 32 AF XY: 0.0971 AC XY: 7221 AN XY: 74392

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.0347

Gnomad4 NFE AF: 0.0571

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.0650 Hom.: 397

Bravo AF: 0.0992

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.4
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10875990; hg19: chr12-50372026;