NM_006908.5:c.448+30T>C

Variant names:

• chr7-6402057-T-C
• rs2303364
• NM_006908.5:c.448+30T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 48

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Illumina, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006908.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	NM_006908.5	MANE Select	c.448+30T>C		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.505+30T>C		intron	N/A	NP_061485.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.448+30T>C		intron	N/A	ENSP00000258737.7
	RAC1	ENST00000356142.4	TSL:1	c.505+30T>C		intron	N/A	ENSP00000348461.4
	RAC1	ENST00000488373.5	TSL:1	n.679+30T>C		intron	N/A

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

GnomAD2 exomes AF: 0.117 AC: 28087 AN: 240192 AF XY: 0.117

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 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

African (AFR) AF: 0.0267 AC: 887 AN: 33208

American (AMR) AF: 0.113 AC: 4926 AN: 43642

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 1804 AN: 25178

East Asian (EAS) AF: 0.542 AC: 21440 AN: 39584

South Asian (SAS) AF: 0.194 AC: 16355 AN: 84444

European-Finnish (FIN) AF: 0.105 AC: 5545 AN: 52786

Middle Eastern (MID) AF: 0.0577 AC: 328 AN: 5684

European-Non Finnish (NFE) AF: 0.0422 AC: 46698 AN: 1105826

Other (OTH) AF: 0.0840 AC: 5034 AN: 59912

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

African (AFR) AF: 0.0287 AC: 1191 AN: 41554

American (AMR) AF: 0.115 AC: 1760 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2601 AN: 5140

South Asian (SAS) AF: 0.213 AC: 1024 AN: 4814

European-Finnish (FIN) AF: 0.115 AC: 1219 AN: 10602

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0462 AC: 3144 AN: 67984

Other (OTH) AF: 0.0873 AC: 184 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.74
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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