7-6395273-G-A

Variant names:

• chr7-6395273-G-A
• rs836472
• NM_006908.5:c.225+3232G>A

Variant summary

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

The NM_006908.5(RAC1):​c.225+3232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,810 control chromosomes in the GnomAD database, including 7,361 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 0.29 (7361 hom., cov: 32)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.225+3232G>A		intron_variant	Intron 3 of 5	ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.225+3232G>A		intron_variant	Intron 3 of 6		NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.225+3232G>A		intron_variant	Intron 3 of 5	1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44524 AN: 151694 Hom.: 7335 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.294 AC: 44582 AN: 151810 Hom.: 7361 Cov.: 32 AF XY: 0.301 AC XY: 22298 AN XY: 74202

African (AFR) AF: 0.285 AC: 11803 AN: 41362

American (AMR) AF: 0.322 AC: 4900 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3472

East Asian (EAS) AF: 0.783 AC: 4035 AN: 5150

South Asian (SAS) AF: 0.427 AC: 2054 AN: 4814

European-Finnish (FIN) AF: 0.292 AC: 3088 AN: 10578

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17358 AN: 67888

Other (OTH) AF: 0.281 AC: 591 AN: 2104

Alfa AF: 0.267 Hom.: 26050

Bravo AF: 0.294

Asia WGS AF: 0.624 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.4
DANN	Benign	0.75
PhyloP100		0.12
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: rs836472; hg19: chr7-6434904;