rs4821615

Variant names:

• chr22-37250091-G-C
• rs4821615
• ENST00000699915.1:n.94-8433C>G

Variant summary

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

The ENST00000699915.1(RAC2):​n.94-8433C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,970 control chromosomes in the GnomAD database, including 21,411 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 0.51 (21411 hom., cov: 32)
• Consequence: RAC2 ENST00000699915.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 4 publications found

Genes affected

RAC2 (HGNC:9802): (Rac family small GTPase 2) This gene encodes a member of the Ras superfamily of small guanosine triphosphate (GTP)-metabolizing proteins. The encoded protein localizes to the plasma membrane, where it regulates diverse processes, such as secretion, phagocytosis, and cell polarization. Activity of this protein is also involved in the generation of reactive oxygen species. Mutations in this gene are associated with neutrophil immunodeficiency syndrome. There is a pseudogene for this gene on chromosome 6. [provided by RefSeq, Jul 2013]

RAC2 Gene-Disease associations (from GenCC):

• immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• neutrophil immunodeficiency syndrome

  Inheritance: Unknown, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699915.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	ENST00000699915.1		n.94-8433C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.514 AC: 77988 AN: 151852 Hom.: 21378 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.514 AC: 78082 AN: 151970 Hom.: 21411 Cov.: 32 AF XY: 0.508 AC XY: 37685 AN XY: 74254

African (AFR) AF: 0.715 AC: 29626 AN: 41452

American (AMR) AF: 0.414 AC: 6324 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1604 AN: 3464

East Asian (EAS) AF: 0.416 AC: 2152 AN: 5176

South Asian (SAS) AF: 0.463 AC: 2232 AN: 4818

European-Finnish (FIN) AF: 0.412 AC: 4335 AN: 10520

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30293 AN: 67938

Other (OTH) AF: 0.491 AC: 1039 AN: 2114

Alfa AF: 0.477 Hom.: 2274

Bravo AF: 0.521

Asia WGS AF: 0.448 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.31
DANN	Benign	0.26
PhyloP100		-2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4821615; hg19: chr22-37646131;