rs3729790

chr7-6387323-G-Achr7-6387323-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.107+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,340,934 control chromosomes in the GnomAD database, including 31,978 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 0.17 (2516 hom., cov: 32)
  • Exomes 𝑓: 0.22 (29462 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.33

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC1	NM_006908.5	c.107+40G>A		intron_variant		ENST00000348035.9
RAC1	NM_018890.4	c.107+40G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC1	ENST00000348035.9	c.107+40G>A		intron_variant		1	NM_006908.5	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25547 AN: 151990 Hom.: 2516 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0958

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.153

GnomAD3 exomes AF: 0.182 AC: 36771 AN: 202566 Hom.: 3742 AF XY: 0.182 AC XY: 20222 AN XY: 111162

Gnomad AFR exome AF: 0.0706

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.0922

Gnomad EAS exome AF: 0.217

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.216 AC: 256593 AN: 1188826 Hom.: 29462 Cov.: 16 AF XY: 0.213 AC XY: 128342 AN XY: 602698

Gnomad4 AFR exome AF: 0.0642

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.0995

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.168 AC: 25550 AN: 152108 Hom.: 2516 Cov.: 32 AF XY: 0.165 AC XY: 12262 AN XY: 74352

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.0958

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.154

Alfa AF: 0.185 Hom.: 2182

Bravo AF: 0.164

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.25
Dann	Benign	0.29
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

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: rs3729790; hg19: chr7-6426954; COSMIC: COSV61821777; COSMIC: COSV61821777;