12-50000635-C-T

Position:

• chr12-50000635-C-T

Variant summary

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

The NM_001319999.2(RACGAP1):​c.630+537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,230 control chromosomes in the GnomAD database, including 68,498 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 0.95 (68498 hom., cov: 31)
• Consequence: RACGAP1 NM_001319999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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]

RACGAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RACGAP1	NM_001319999.2	c.630+537G>A		intron_variant		ENST00000312377.10	NP_001306928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RACGAP1	ENST00000312377.10	c.630+537G>A		intron_variant		1	NM_001319999.2	ENSP00000309871.5

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143840 AN: 152112 Hom.: 68450 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.958

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

GnomAD4 genome AF: 0.946 AC: 143948 AN: 152230 Hom.: 68498 Cov.: 31 AF XY: 0.947 AC XY: 70487 AN XY: 74424

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.959

Alfa AF: 0.968 Hom.: 4722

Bravo AF: 0.938

Asia WGS AF: 0.987 AC: 3434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.8
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1967110; hg19: chr12-50394418;