7-6404208-T-C

Variant names:

• chr7-6404208-T-C
• rs4720672
• NM_006908.5:c.*1762T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006908.5(RAC1):​c.*1762T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,180 control chromosomes in the GnomAD database, including 1,615 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 (1615 hom., cov: 32)
• Consequence: RAC1 NM_006908.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 25 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):

• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 48

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	NM_006908.5	MANE Select	c.*1762T>C		downstream_gene	N/A	NP_008839.2
	RAC1	NM_018890.4		c.*1762T>C		downstream_gene	N/A	NP_061485.1	P63000-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.*1762T>C		downstream_gene	N/A	ENSP00000258737.7	P63000-1
	RAC1	ENST00000887276.1		c.*1762T>C		downstream_gene	N/A	ENSP00000557335.1
	RAC1	ENST00000966157.1		c.*1762T>C		downstream_gene	N/A	ENSP00000636216.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20788 AN: 152062 Hom.: 1614 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.137 AC: 20795 AN: 152180 Hom.: 1615 Cov.: 32 AF XY: 0.136 AC XY: 10131 AN XY: 74400

African (AFR) AF: 0.0626 AC: 2599 AN: 41536

American (AMR) AF: 0.130 AC: 1988 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.167 AC: 861 AN: 5164

South Asian (SAS) AF: 0.140 AC: 675 AN: 4820

European-Finnish (FIN) AF: 0.201 AC: 2131 AN: 10588

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11912 AN: 68000

Other (OTH) AF: 0.132 AC: 278 AN: 2110

Alfa AF: 0.159 Hom.: 3231

Bravo AF: 0.132

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		-0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4720672; hg19: chr7-6443839; COSMIC: COSV51705353;