7-6399287-G-T

Variant names:

• chr7-6399287-G-T
• rs836547
• NM_006908.5:c.226-839G>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.226-839G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,186 control chromosomes in the GnomAD database, including 3,052 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 (3052 hom., cov: 33)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.226-839G>T		intron_variant	Intron 3 of 5	ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.282+569G>T		intron_variant	Intron 4 of 6		NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.226-839G>T		intron_variant	Intron 3 of 5	1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26064 AN: 152068 Hom.: 3029 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.172 AC: 26125 AN: 152186 Hom.: 3052 Cov.: 33 AF XY: 0.181 AC XY: 13463 AN XY: 74402

African (AFR) AF: 0.249 AC: 10356 AN: 41518

American (AMR) AF: 0.200 AC: 3049 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3470

East Asian (EAS) AF: 0.536 AC: 2770 AN: 5170

South Asian (SAS) AF: 0.279 AC: 1346 AN: 4830

European-Finnish (FIN) AF: 0.161 AC: 1702 AN: 10580

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0903 AC: 6142 AN: 68024

Other (OTH) AF: 0.164 AC: 346 AN: 2116

Alfa AF: 0.122 Hom.: 348

Bravo AF: 0.173

Asia WGS AF: 0.422 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.2
DANN	Benign	0.85
PhyloP100		-0.097
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: rs836547; hg19: chr7-6438918;