NM_006908.5:c.*294G>A

Variant names:

• chr7-6402740-G-A
• rs9374
• NM_006908.5:c.*294G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 48

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Illumina, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006908.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	NM_006908.5	MANE Select	c.*294G>A		3_prime_UTR	Exon 6 of 6	NP_008839.2
	RAC1	NM_018890.4		c.*294G>A		3_prime_UTR	Exon 7 of 7	NP_061485.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.*294G>A		3_prime_UTR	Exon 6 of 6	ENSP00000258737.7
	RAC1	ENST00000704003.1		n.*826G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000515616.1
	RAC1	ENST00000704003.1		n.*826G>A		3_prime_UTR	Exon 7 of 7	ENSP00000515616.1

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

African (AFR) AF: 0.0702 AC: 285 AN: 4062

American (AMR) AF: 0.156 AC: 741 AN: 4764

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 512 AN: 5536

East Asian (EAS) AF: 0.202 AC: 2194 AN: 10886

South Asian (SAS) AF: 0.127 AC: 961 AN: 7590

European-Finnish (FIN) AF: 0.215 AC: 662 AN: 3082

Middle Eastern (MID) AF: 0.117 AC: 70 AN: 598

European-Non Finnish (NFE) AF: 0.211 AC: 15424 AN: 73182

Other (OTH) AF: 0.184 AC: 1480 AN: 8048

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

African (AFR) AF: 0.0730 AC: 3024 AN: 41444

American (AMR) AF: 0.156 AC: 2381 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1191 AN: 5140

South Asian (SAS) AF: 0.150 AC: 722 AN: 4806

European-Finnish (FIN) AF: 0.265 AC: 2783 AN: 10486

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15971 AN: 67944

Other (OTH) AF: 0.163 AC: 343 AN: 2108

Alfa AF: 0.210 Hom.: 5087

Bravo AF: 0.169

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9374; hg19: chr7-6442371;