rs35761891

chr7-6398586-A-G

Variant summary

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

The NM_006908.5(RAC1):c.226-1540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,279,172 control chromosomes in the GnomAD database, including 1,524 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 0.036 (147 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1377 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

Genes affected

RAC1 (HGNC:9801): (Rac family small GTPase 1) The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC1	NM_006908.5	c.226-1540A>G		intron_variant		ENST00000348035.9
RAC1	NM_018890.4	c.226-76A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC1	ENST00000348035.9	c.226-1540A>G		intron_variant		1	NM_006908.5	P1

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5526 AN: 152190 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.00837

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0196

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.0445 AC: 50160 AN: 1126864 Hom.: 1377 AF XY: 0.0446 AC XY: 25511 AN XY: 571822

Gnomad4 AFR exome AF: 0.00724

Gnomad4 AMR exome AF: 0.0331

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0000833

Gnomad4 SAS exome AF: 0.0217

Gnomad4 FIN exome AF: 0.0451

Gnomad4 NFE exome AF: 0.0479

Gnomad4 OTH exome AF: 0.0465

GnomAD4 genome AF: 0.0363 AC: 5529 AN: 152308 Hom.: 147 Cov.: 32 AF XY: 0.0348 AC XY: 2588 AN XY: 74470

Gnomad4 AFR AF: 0.00835

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0415 Hom.: 28

Bravo AF: 0.0345

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.91
Dann	Benign	0.70

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: rs35761891; hg19: chr7-6438217;