chr7-6387323-G-A

Variant names:

• chr7-6387323-G-A
• rs3729790
• NM_006908.5:c.107+40G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006908.5(RAC1):​c.107+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,340,934 control chromosomes in the GnomAD database, including 31,978 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 0.17 (2516 hom., cov: 32)
  • Exomes 𝑓: 0.22 (29462 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.33
• Publications: 20 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 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.107+40G>A		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.107+40G>A		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.107+40G>A		intron	N/A	ENSP00000258737.7
	RAC1	ENST00000356142.4	TSL:1	c.107+40G>A		intron	N/A	ENSP00000348461.4
	RAC1	ENST00000488373.5	TSL:1	n.338+40G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25547 AN: 151990 Hom.: 2516 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0958

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.182 AC: 36771 AN: 202566 AF XY: 0.182

Gnomad AFR exome AF: 0.0706

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.0922

Gnomad EAS exome AF: 0.217

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.216 AC: 256593 AN: 1188826 Hom.: 29462 Cov.: 16 AF XY: 0.213 AC XY: 128342 AN XY: 602698

African (AFR) AF: 0.0642 AC: 1591 AN: 24792

American (AMR) AF: 0.160 AC: 4808 AN: 29966

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 2328 AN: 23398

East Asian (EAS) AF: 0.211 AC: 7471 AN: 35448

South Asian (SAS) AF: 0.145 AC: 10620 AN: 73004

European-Finnish (FIN) AF: 0.201 AC: 10568 AN: 52614

Middle Eastern (MID) AF: 0.113 AC: 591 AN: 5232

European-Non Finnish (NFE) AF: 0.233 AC: 208135 AN: 893324

Other (OTH) AF: 0.205 AC: 10481 AN: 51048

GnomAD4 genome AF: 0.168 AC: 25550 AN: 152108 Hom.: 2516 Cov.: 32 AF XY: 0.165 AC XY: 12262 AN XY: 74352

African (AFR) AF: 0.0722 AC: 2997 AN: 41490

American (AMR) AF: 0.152 AC: 2316 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0958 AC: 332 AN: 3466

East Asian (EAS) AF: 0.232 AC: 1203 AN: 5178

South Asian (SAS) AF: 0.152 AC: 734 AN: 4826

European-Finnish (FIN) AF: 0.198 AC: 2095 AN: 10564

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15431 AN: 67994

Other (OTH) AF: 0.154 AC: 326 AN: 2116

Alfa AF: 0.173 Hom.: 3613

Bravo AF: 0.164

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.29
PhyloP100		-5.3
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
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: rs3729790; hg19: chr7-6426954; COSMIC: COSV61821777; COSMIC: COSV61821777;