7-6392302-C-G

Variant names:

• chr7-6392302-C-G
• rs702484
• NM_006908.5:c.225+261C>G

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+261C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,008 control chromosomes in the GnomAD database, including 10,385 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 0.35 (10385 hom., cov: 32)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.225+261C>G		intron_variant	Intron 3 of 5	ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.225+261C>G		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+261C>G		intron_variant	Intron 3 of 5	1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53598 AN: 151890 Hom.: 10346 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.353 AC: 53693 AN: 152008 Hom.: 10385 Cov.: 32 AF XY: 0.362 AC XY: 26906 AN XY: 74334

African (AFR) AF: 0.357 AC: 14781 AN: 41460

American (AMR) AF: 0.477 AC: 7278 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3468

East Asian (EAS) AF: 0.794 AC: 4103 AN: 5170

South Asian (SAS) AF: 0.464 AC: 2234 AN: 4812

European-Finnish (FIN) AF: 0.333 AC: 3527 AN: 10576

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20023 AN: 67968

Other (OTH) AF: 0.345 AC: 727 AN: 2108

Alfa AF: 0.190 Hom.: 398

Bravo AF: 0.366

Asia WGS AF: 0.652 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.34
PhyloP100		-0.62
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: rs702484; hg19: chr7-6431933;