22-37249190-A-G

Position:

• chr22-37249190-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699915.1(RAC2):​n.94-7532T>C variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC2	ENST00000699915.1	n.94-7532T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.498

Alfa AF: 0.450 Hom.: 26281

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs739043; hg19: chr22-37645230;