rs7288979

chr22-37253454-T-Cchr22-37253454-T-G

Variant summary

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

The ENST00000699915.1(RAC2):n.93+6048A>G 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 0.144 in 152,208 control chromosomes in the GnomAD database, including 1,706 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 0.14 (1706 hom., cov: 32)
• Consequence: RAC2 ENST00000699915.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 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.93+6048A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21978 AN: 152090 Hom.: 1707 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.144 AC: 21976 AN: 152208 Hom.: 1706 Cov.: 32 AF XY: 0.140 AC XY: 10454 AN XY: 74416

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0756

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.146

Alfa AF: 0.171 Hom.: 3850

Bravo AF: 0.141

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.7
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: rs7288979; hg19: chr22-37649494;