rs9374

chr7-6402740-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006908.5(RAC1):c.*294G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 269,590 control chromosomes in the GnomAD database, including 5,233 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 0.18 (2801 hom., cov: 31)
  • Exomes 𝑓: 0.19 (2432 hom.)
• Consequence: RAC1 NM_006908.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC1	NM_006908.5	c.*294G>A		3_prime_UTR_variant	6/6	ENST00000348035.9
RAC1	NM_018890.4	c.*294G>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC1	ENST00000348035.9	c.*294G>A		3_prime_UTR_variant	6/6	1	NM_006908.5	P1
RAC1	ENST00000704003.1	c.*826G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26870 AN: 151722 Hom.: 2800 Cov.: 31

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.190 AC: 22329 AN: 117748 Hom.: 2432 Cov.: 3 AF XY: 0.186 AC XY: 11008 AN XY: 59096

Gnomad4 AFR exome AF: 0.0702

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.0925

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.177 AC: 26875 AN: 151842 Hom.: 2801 Cov.: 31 AF XY: 0.176 AC XY: 13070 AN XY: 74166

Gnomad4 AFR AF: 0.0730

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.163

Alfa AF: 0.213 Hom.: 3578

Bravo AF: 0.169

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	15
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9374; hg19: chr7-6442371;