chr7-6398170-G-C

Variant names:

• chr7-6398170-G-C
• rs6463554
• NM_006908.5:c.226-1956G>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.226-1956G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,074 control chromosomes in the GnomAD database, including 1,792 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 (1792 hom., cov: 32)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 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.226-1956G>C		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.226-492G>C		intron	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.226-1956G>C		intron	N/A	ENSP00000258737.7	P63000-1
	RAC1	ENST00000356142.4	TSL:1	c.226-492G>C		intron	N/A	ENSP00000348461.4	P63000-2
	RAC1	ENST00000488373.5	TSL:1	n.457-1956G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21919 AN: 151956 Hom.: 1785 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.144 AC: 21941 AN: 152074 Hom.: 1792 Cov.: 32 AF XY: 0.144 AC XY: 10681 AN XY: 74336

African (AFR) AF: 0.156 AC: 6478 AN: 41472

American (AMR) AF: 0.224 AC: 3423 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3470

East Asian (EAS) AF: 0.0145 AC: 75 AN: 5168

South Asian (SAS) AF: 0.0635 AC: 306 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1373 AN: 10586

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9326 AN: 67982

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.152 Hom.: 222

Bravo AF: 0.154

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		0.44
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: rs6463554; hg19: chr7-6437801;