ENST00000699915.1:n.94-7532T>C

Variant names:

• chr22-37249190-A-G
• rs739043
• ENST00000699915.1:n.94-7532T>C

Variant summary

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

The ENST00000699915.1(RAC2):​n.94-7532T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,910 control chromosomes in the GnomAD database, including 21,592 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 0.52 (21592 hom., cov: 32)
• Consequence: RAC2 ENST00000699915.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000699915.1	n.94-7532T>C		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78297 AN: 151792 Hom.: 21558 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.516 AC: 78393 AN: 151910 Hom.: 21592 Cov.: 32 AF XY: 0.510 AC XY: 37848 AN XY: 74244

African (AFR) AF: 0.718 AC: 29775 AN: 41444

American (AMR) AF: 0.417 AC: 6373 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1601 AN: 3460

East Asian (EAS) AF: 0.425 AC: 2191 AN: 5154

South Asian (SAS) AF: 0.464 AC: 2228 AN: 4806

European-Finnish (FIN) AF: 0.411 AC: 4328 AN: 10536

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.447 AC: 30372 AN: 67930

Other (OTH) AF: 0.498 AC: 1046 AN: 2102

Alfa AF: 0.464 Hom.: 65222

Bravo AF: 0.525

Asia WGS AF: 0.450 AC: 1565 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	0.15
DANN	Benign	0.37
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs739043; hg19: chr22-37645230;