rs10875990

Variant names:

• chr12-49978243-C-T
• rs10875990
• ENST00000548961.5:c.245-1184G>A

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RACGAP1	ENST00000548961.5	c.245-1184G>A		intron_variant	Intron 2 of 2	3		ENSP00000446889.1

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;