7-6395589-G-C

Variant names:

• chr7-6395589-G-C
• rs1880118
• NM_006908.5:c.225+3548G>C

Variant summary

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

The ENST00000348035.9(RAC1):​c.225+3548G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,192 control chromosomes in the GnomAD database, including 2,509 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 (2509 hom., cov: 32)
• Consequence: RAC1 ENST00000348035.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000348035.9. 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.225+3548G>C		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.226-3073G>C		intron	N/A	NP_061485.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.225+3548G>C		intron	N/A	ENSP00000258737.7
	RAC1	ENST00000356142.4	TSL:1	c.226-3073G>C		intron	N/A	ENSP00000348461.4
	RAC1	ENST00000488373.5	TSL:1	n.456+3548G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25624 AN: 152074 Hom.: 2508 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.168 AC: 25629 AN: 152192 Hom.: 2509 Cov.: 32 AF XY: 0.165 AC XY: 12291 AN XY: 74386

African (AFR) AF: 0.0740 AC: 3073 AN: 41542

American (AMR) AF: 0.154 AC: 2360 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1203 AN: 5182

South Asian (SAS) AF: 0.152 AC: 733 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10588

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15431 AN: 67976

Other (OTH) AF: 0.155 AC: 328 AN: 2116

Alfa AF: 0.191 Hom.: 365

Bravo AF: 0.166

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		-0.17
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: rs1880118; hg19: chr7-6435220;