rs836479

Variant names:

• chr7-6391789-C-A
• rs836479
• NM_006908.5:c.108-135C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-6391789-C-A
• chr7-6391789-C-G
• chr7-6391789-C-T

Variant summary

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

The NM_006908.5(RAC1):​c.108-135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,410,936 control chromosomes in the GnomAD database, including 18,930 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 (3595 hom., cov: 32)
  • Exomes 𝑓: 0.10 (15335 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 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.108-135C>A		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.108-135C>A		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.108-135C>A		intron	N/A	ENSP00000258737.7	P63000-1
	RAC1	ENST00000356142.4	TSL:1	c.108-135C>A		intron	N/A	ENSP00000348461.4	P63000-2
	RAC1	ENST00000488373.5	TSL:1	n.339-135C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26403 AN: 151942 Hom.: 3565 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.104 AC: 131545 AN: 1258876 Hom.: 15335 AF XY: 0.107 AC XY: 66414 AN XY: 619246

African (AFR) AF: 0.250 AC: 7092 AN: 28384

American (AMR) AF: 0.398 AC: 11470 AN: 28806

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 2057 AN: 19690

East Asian (EAS) AF: 0.594 AC: 21353 AN: 35960

South Asian (SAS) AF: 0.269 AC: 16955 AN: 63100

European-Finnish (FIN) AF: 0.121 AC: 5076 AN: 41882

Middle Eastern (MID) AF: 0.101 AC: 358 AN: 3556

European-Non Finnish (NFE) AF: 0.0610 AC: 60102 AN: 985050

Other (OTH) AF: 0.135 AC: 7082 AN: 52448

GnomAD4 genome AF: 0.174 AC: 26487 AN: 152060 Hom.: 3595 Cov.: 32 AF XY: 0.186 AC XY: 13804 AN XY: 74308

African (AFR) AF: 0.249 AC: 10341 AN: 41476

American (AMR) AF: 0.322 AC: 4905 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3468

East Asian (EAS) AF: 0.560 AC: 2885 AN: 5156

South Asian (SAS) AF: 0.297 AC: 1430 AN: 4820

European-Finnish (FIN) AF: 0.134 AC: 1412 AN: 10560

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0670 AC: 4559 AN: 68010

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.125 Hom.: 1563

Bravo AF: 0.189

Asia WGS AF: 0.445 AC: 1542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.97
DANN	Benign	0.66
PhyloP100		-0.086
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: rs836479; hg19: chr7-6431420;