rs6954996

Positions:

• chr7-6401627-G-A
• chr7-6401627-G-T

Variant summary

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

The ENST00000348035.9(RAC1):​c.289-241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 322,038 control chromosomes in the GnomAD database, including 1,077 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 0.079 (843 hom., cov: 32)
  • Exomes 𝑓: 0.042 (234 hom.)
• Consequence: RAC1 ENST00000348035.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC1	NM_006908.5	c.289-241G>A		intron_variant		ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.346-241G>A		intron_variant			NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.289-241G>A		intron_variant		1	NM_006908.5	ENSP00000258737	P1

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 11988 AN: 152022 Hom.: 843 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0316

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0421 AC: 7160 AN: 169896 Hom.: 234 Cov.: 3 AF XY: 0.0422 AC XY: 3640 AN XY: 86184

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.0284

Gnomad4 ASJ exome AF: 0.0459

Gnomad4 EAS exome AF: 0.0641

Gnomad4 SAS exome AF: 0.0913

Gnomad4 FIN exome AF: 0.0356

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.0548

GnomAD4 genome AF: 0.0789 AC: 11998 AN: 152142 Hom.: 843 Cov.: 32 AF XY: 0.0790 AC XY: 5875 AN XY: 74390

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0370

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.0880

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0316

Gnomad4 OTH AF: 0.0606

Alfa AF: 0.0197 Hom.: 7

Bravo AF: 0.0830

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6954996; hg19: chr7-6441258;