22-37248075-T-C

Variant names:

• chr22-37248075-T-C
• rs6000632
• ENST00000699915.1:n.94-6417A>G

Variant summary

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

The ENST00000699915.1(RAC2):​n.94-6417A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,074 control chromosomes in the GnomAD database, including 46,475 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 0.78 (46475 hom., cov: 31)
• Consequence: RAC2 ENST00000699915.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 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.94-6417A>G		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118189 AN: 151956 Hom.: 46408 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.778 AC: 118323 AN: 152074 Hom.: 46475 Cov.: 31 AF XY: 0.775 AC XY: 57612 AN XY: 74324

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.783

Alfa AF: 0.759 Hom.: 44179

Bravo AF: 0.784

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6000632; hg19: chr22-37644115;