rs12536544

Positions:

• chr7-6396270-G-A

Variant summary

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

The NM_006908.5(RAC1):​c.226-3856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,028 control chromosomes in the GnomAD database, including 5,623 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 0.24 (5623 hom., cov: 31)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

RAC1 (HGNC:9801): (Rac family small GTPase 1) The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

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 = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC1	NM_006908.5	c.226-3856G>A		intron_variant		ENST00000348035.9
RAC1	NM_018890.4	c.226-2392G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC1	ENST00000348035.9	c.226-3856G>A		intron_variant		1	NM_006908.5	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36856 AN: 151910 Hom.: 5619 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.242 AC: 36864 AN: 152028 Hom.: 5623 Cov.: 31 AF XY: 0.251 AC XY: 18674 AN XY: 74322

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.235

Alfa AF: 0.249 Hom.: 800

Bravo AF: 0.230

Asia WGS AF: 0.551 AC: 1911 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	0.065
DANN	Benign	0.75

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: rs12536544; hg19: chr7-6435901;