chr7-6404208-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.*1762T>C		downstream_gene_variant		ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.*1762T>C		downstream_gene_variant			NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.*1762T>C		downstream_gene_variant		1	NM_006908.5	ENSP00000258737.7
RAC1	ENST00000704003.1	n.*2294T>C		downstream_gene_variant				ENSP00000515616.1

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

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.132

Alfa AF: 0.160 Hom.: 2241

Bravo AF: 0.132

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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