rs6463554

Positions:

• chr7-6398170-G-C

Variant summary

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

The NM_006908.5(RAC1):​c.226-1956G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,074 control chromosomes in the GnomAD database, including 1,792 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 0.14 (1792 hom., cov: 32)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

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]

RAC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC1	NM_006908.5	c.226-1956G>C		intron_variant		ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.226-492G>C		intron_variant			NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.226-1956G>C		intron_variant		1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21919 AN: 151956 Hom.: 1785 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.144 AC: 21941 AN: 152074 Hom.: 1792 Cov.: 32 AF XY: 0.144 AC XY: 10681 AN XY: 74336

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.0145

Gnomad4 SAS AF: 0.0635

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.151

Alfa AF: 0.152 Hom.: 222

Bravo AF: 0.154

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.64

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: rs6463554; hg19: chr7-6437801;