rs836475

Positions:

• chr7-6394301-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.225+2260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 152,236 control chromosomes in the GnomAD database, including 532 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 0.054 (532 hom., cov: 32)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC1	NM_006908.5	c.225+2260G>A		intron_variant		ENST00000348035.9
RAC1	NM_018890.4	c.225+2260G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC1	ENST00000348035.9	c.225+2260G>A		intron_variant		1	NM_006908.5	P1

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8210 AN: 152118 Hom.: 528 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0541 AC: 8232 AN: 152236 Hom.: 532 Cov.: 32 AF XY: 0.0547 AC XY: 4070 AN XY: 74452

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.0543

Gnomad4 SAS AF: 0.0639

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00259

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0229 Hom.: 78

Bravo AF: 0.0618

Asia WGS AF: 0.0680 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.77

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: rs836475; hg19: chr7-6433932;