chr22-37236730-T-A

Position:

• chr22-37236730-T-A

Variant summary

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

The ENST00000249071.11(RAC2):​c.108-3812A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,916 control chromosomes in the GnomAD database, including 3,350 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 0.20 (3350 hom., cov: 32)
• Consequence: RAC2 ENST00000249071.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC2	NM_002872.5	c.108-3812A>T		intron_variant		ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.108-3812A>T		intron_variant			XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.108-3812A>T		intron_variant		1	NM_002872.5	ENSP00000249071	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30491 AN: 151796 Hom.: 3349 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.201 AC: 30511 AN: 151916 Hom.: 3350 Cov.: 32 AF XY: 0.199 AC XY: 14809 AN XY: 74252

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0887

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.203

Alfa AF: 0.113 Hom.: 205

Bravo AF: 0.197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs13058338; hg19: chr22-37632770;