7-6380363-A-T

Variant names:

• chr7-6380363-A-T
• rs10499343
• NM_006908.5:c.35+5593A>T

Variant summary

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

The NM_006908.5(RAC1):​c.35+5593A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 141,454 control chromosomes in the GnomAD database, including 1,802 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 0.16 (1802 hom., cov: 33)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586
• Publications: 5 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):

• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 48

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	NM_006908.5	MANE Select	c.35+5593A>T		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.35+5593A>T		intron	N/A	NP_061485.1	P63000-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.35+5593A>T		intron	N/A	ENSP00000258737.7	P63000-1
	RAC1	ENST00000356142.4	TSL:1	c.35+5593A>T		intron	N/A	ENSP00000348461.4	P63000-2
	RAC1	ENST00000488373.5	TSL:1	n.266+4447A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.155 AC: 21974 AN: 141344 Hom.: 1795 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.0157

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.159

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 21994 AN: 141454 Hom.: 1802 Cov.: 33 AF XY: 0.155 AC XY: 10702 AN XY: 69080

African (AFR) AF: 0.189 AC: 6480 AN: 34226

American (AMR) AF: 0.234 AC: 3422 AN: 14624

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 316 AN: 3440

East Asian (EAS) AF: 0.0159 AC: 77 AN: 4838

South Asian (SAS) AF: 0.0695 AC: 306 AN: 4400

European-Finnish (FIN) AF: 0.134 AC: 1370 AN: 10222

Middle Eastern (MID) AF: 0.128 AC: 37 AN: 290

European-Non Finnish (NFE) AF: 0.141 AC: 9360 AN: 66482

Other (OTH) AF: 0.157 AC: 319 AN: 2028

Alfa AF: 0.146 Hom.: 214

Bravo AF: 0.155

Asia WGS AF: 0.0520 AC: 180 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.70
PhyloP100		-0.59
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: rs10499343; hg19: chr7-6419994;