rs836478

Variant names:

• chr7-6392059-C-T
• rs836478
• NM_006908.5:c.225+18C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-6392059-C-T
• chr7-6392059-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006908.5(RAC1):​c.225+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,613,614 control chromosomes in the GnomAD database, including 218,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (26069 hom., cov: 32)
  • Exomes 𝑓: 0.50 (192497 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39
• Publications: 27 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 7-6392059-C-T is Benign according to our data. Variant chr7-6392059-C-T is described in ClinVar as Benign. ClinVar VariationId is 1327930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 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.225+18C>T		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.225+18C>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.225+18C>T		intron	N/A	ENSP00000258737.7	P63000-1
	RAC1	ENST00000356142.4	TSL:1	c.225+18C>T		intron	N/A	ENSP00000348461.4	P63000-2
	RAC1	ENST00000488373.5	TSL:1	n.456+18C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86584 AN: 151868 Hom.: 26019 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.540

GnomAD2 exomes AF: 0.562 AC: 141158 AN: 251230 AF XY: 0.551

Gnomad AFR exome AF: 0.723

Gnomad AMR exome AF: 0.704

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.911

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.503 AC: 735385 AN: 1461628 Hom.: 192497 Cov.: 50 AF XY: 0.504 AC XY: 366140 AN XY: 727068

African (AFR) AF: 0.725 AC: 24282 AN: 33478

American (AMR) AF: 0.694 AC: 31014 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 9972 AN: 26128

East Asian (EAS) AF: 0.906 AC: 35972 AN: 39696

South Asian (SAS) AF: 0.615 AC: 53015 AN: 86222

European-Finnish (FIN) AF: 0.472 AC: 25198 AN: 53400

Middle Eastern (MID) AF: 0.445 AC: 2567 AN: 5768

European-Non Finnish (NFE) AF: 0.469 AC: 521108 AN: 1111836

Other (OTH) AF: 0.534 AC: 32257 AN: 60382

GnomAD4 genome AF: 0.570 AC: 86694 AN: 151986 Hom.: 26069 Cov.: 32 AF XY: 0.575 AC XY: 42697 AN XY: 74276

African (AFR) AF: 0.716 AC: 29703 AN: 41460

American (AMR) AF: 0.625 AC: 9540 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3470

East Asian (EAS) AF: 0.909 AC: 4707 AN: 5178

South Asian (SAS) AF: 0.639 AC: 3084 AN: 4826

European-Finnish (FIN) AF: 0.474 AC: 4992 AN: 10538

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31651 AN: 67950

Other (OTH) AF: 0.546 AC: 1155 AN: 2114

Alfa AF: 0.522 Hom.: 4800

Bravo AF: 0.590

Asia WGS AF: 0.809 AC: 2812 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability, autosomal dominant 48 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.4
DANN	Benign	0.87
PhyloP100		-1.4
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: rs836478; hg19: chr7-6431690; COSMIC: COSV107421691;