7-6402057-T-C

Position:

• chr7-6402057-T-C

Variant summary

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

The NM_006908.5(RAC1):​c.448+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 1,602,402 control chromosomes in the GnomAD database, including 10,798 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 0.076 (1082 hom., cov: 32)
  • Exomes 𝑓: 0.071 (9716 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383

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]

RAC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC1	NM_006908.5	c.448+30T>C		intron_variant		ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.505+30T>C		intron_variant			NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.448+30T>C		intron_variant		1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11545 AN: 152020 Hom.: 1081 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0825

GnomAD3 exomes AF: 0.117 AC: 28087 AN: 240192 Hom.: 3618 AF XY: 0.117 AC XY: 15213 AN XY: 129500

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.0721

Gnomad EAS exome AF: 0.504

Gnomad SAS exome AF: 0.206

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.0475

Gnomad OTH exome AF: 0.0924

GnomAD4 exome AF: 0.0710 AC: 103017 AN: 1450264 Hom.: 9716 Cov.: 30 AF XY: 0.0744 AC XY: 53609 AN XY: 720910

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.0716

Gnomad4 EAS exome AF: 0.542

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0422

Gnomad4 OTH exome AF: 0.0840

GnomAD4 genome AF: 0.0759 AC: 11549 AN: 152138 Hom.: 1082 Cov.: 32 AF XY: 0.0857 AC XY: 6369 AN XY: 74344

Gnomad4 AFR AF: 0.0287

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0873

Alfa AF: 0.0542 Hom.: 100

Bravo AF: 0.0708

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.74

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: rs2303364; hg19: chr7-6441688; COSMIC: COSV61823789;