rs836488

Variant names:

• chr7-6380162-C-T
• rs836488
• NM_006908.5:c.35+5392C>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+5392C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,134 control chromosomes in the GnomAD database, including 2,555 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 0.13 (2555 hom., cov: 33)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.35+5392C>T		intron_variant	Intron 1 of 5	ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.35+5392C>T		intron_variant	Intron 1 of 6		NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.35+5392C>T		intron_variant	Intron 1 of 5	1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20036 AN: 152016 Hom.: 2533 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.132 AC: 20097 AN: 152134 Hom.: 2555 Cov.: 33 AF XY: 0.142 AC XY: 10553 AN XY: 74362

African (AFR) AF: 0.236 AC: 9773 AN: 41486

American (AMR) AF: 0.170 AC: 2600 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 280 AN: 3472

East Asian (EAS) AF: 0.560 AC: 2883 AN: 5152

South Asian (SAS) AF: 0.276 AC: 1333 AN: 4824

European-Finnish (FIN) AF: 0.0930 AC: 985 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0286 AC: 1942 AN: 68012

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.0756 Hom.: 116

Bravo AF: 0.136

Asia WGS AF: 0.428 AC: 1484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.84
PhyloP100		-1.5
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: rs836488; hg19: chr7-6419793;