dbSNP rs836479: RAC1:c.108-135C>A (chr7-6391789-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006908.5(RAC1):c.108-135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,410,936 control chromosomes in the GnomAD database, including 18,930 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 ( 3595 hom., cov: 32)

Exomes 𝑓: 0.10 ( 15335 hom. )

Consequence

RAC1
NM_006908.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

6 publications found

Variant links:

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

RAC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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 link	c.108-135C>A		intron_variant	Intron 2 of 5	ENST00000348035.9	NP_008839.2	P63000-1A4D2P1
RAC1	NM_018890.4 link	c.108-135C>A		intron_variant	Intron 2 of 6		NP_061485.1	P63000-2A4D2P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9 link	c.108-135C>A		intron_variant	Intron 2 of 5	1	NM_006908.5	ENSP00000258737.7		P63000-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26403

AN:

151942

Hom.:

3565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0670

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.104

AC:

131545

AN:

1258876

Hom.:

15335

AF XY:

0.107

AC XY:

66414

AN XY:

619246

show subpopulations

African (AFR)

AF:

0.250

AC:

7092

AN:

28384

American (AMR)

AF:

0.398

AC:

11470

AN:

28806

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

2057

AN:

19690

East Asian (EAS)

AF:

0.594

AC:

21353

AN:

35960

South Asian (SAS)

AF:

0.269

AC:

16955

AN:

63100

European-Finnish (FIN)

AF:

0.121

AC:

5076

AN:

41882

Middle Eastern (MID)

AF:

0.101

AC:

358

AN:

3556

European-Non Finnish (NFE)

AF:

0.0610

AC:

60102

AN:

985050

Other (OTH)

AF:

0.135

AC:

7082

AN:

52448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

4768

9536

14304

19072

23840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2742

5484

8226

10968

13710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.174

AC:

26487

AN:

152060

Hom.:

3595

Cov.:

AF XY:

0.186

AC XY:

13804

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.249

AC:

10341

AN:

41476

American (AMR)

AF:

0.322

AC:

4905

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

374

AN:

3468

East Asian (EAS)

AF:

0.560

AC:

2885

AN:

5156

South Asian (SAS)

AF:

0.297

AC:

1430

AN:

4820

European-Finnish (FIN)

AF:

0.134

AC:

1412

AN:

10560

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0670

AC:

4559

AN:

68010

Other (OTH)

AF:

0.184

AC:

388

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

989

1978

2967

3956

4945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.125

Hom.:

1563

Bravo

AF:

0.189

Asia WGS

AF:

0.445

AC:

1542

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.97

(source)

DANN

Benign

0.66

PhyloP100

-0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over