rs6967221

Positions:

• chr7-6391460-G-A
• chr7-6391460-G-T

Variant summary

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

The NM_006908.5(RAC1):​c.108-464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 160,144 control chromosomes in the GnomAD database, including 1,024 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 0.089 (1005 hom., cov: 32)
  • Exomes 𝑓: 0.047 (19 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC1	NM_006908.5	c.108-464G>A		intron_variant		ENST00000348035.9
RAC1	NM_018890.4	c.108-464G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC1	ENST00000348035.9	c.108-464G>A		intron_variant		1	NM_006908.5	P1

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13539 AN: 151958 Hom.: 1001 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0483

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0683

GnomAD4 exome AF: 0.0470 AC: 379 AN: 8068 Hom.: 19 Cov.: 0 AF XY: 0.0516 AC XY: 212 AN XY: 4106

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0234

Gnomad4 ASJ exome AF: 0.0412

Gnomad4 EAS exome AF: 0.0842

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.0339

Gnomad4 OTH exome AF: 0.0477

GnomAD4 genome AF: 0.0891 AC: 13550 AN: 152076 Hom.: 1005 Cov.: 32 AF XY: 0.0891 AC XY: 6625 AN XY: 74352

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0483

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.0408

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0364 Hom.: 68

Bravo AF: 0.0933

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.69
DANN	Benign	0.66

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: rs6967221; hg19: chr7-6431091;