dbSNP rs6954996: RAC1:c.289-241G>A (chr7-6401627-G-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.289-241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 322,038 control chromosomes in the GnomAD database, including 1,077 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 0.079 ( 843 hom., cov: 32)

Exomes 𝑓: 0.042 ( 234 hom. )

Consequence

RAC1
NM_006908.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

5 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5 link	c.289-241G>A		intron_variant	Intron 4 of 5	ENST00000348035.9	NP_008839.2	P63000-1A4D2P1
RAC1	NM_018890.4 link	c.346-241G>A		intron_variant	Intron 5 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.289-241G>A		intron_variant	Intron 4 of 5	1	NM_006908.5	ENSP00000258737.7		P63000-1

Frequencies

GnomAD3 genomes

AF:

0.0789

AC:

11988

AN:

152022

Hom.:

843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0366

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.0880

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0354

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0316

Gnomad OTH

AF:

0.0612

GnomAD4 exome

AF:

0.0421

AC:

7160

AN:

169896

Hom.:

234

Cov.:

AF XY:

0.0422

AC XY:

3640

AN XY:

86184

show subpopulations

African (AFR)

AF:

0.182

AC:

947

AN:

5210

American (AMR)

AF:

0.0284

AC:

152

AN:

5356

Ashkenazi Jewish (ASJ)

AF:

0.0459

AC:

299

AN:

6520

East Asian (EAS)

AF:

0.0641

AC:

907

AN:

14152

South Asian (SAS)

AF:

0.0913

AC:

620

AN:

6790

European-Finnish (FIN)

AF:

0.0356

AC:

429

AN:

12064

Middle Eastern (MID)

AF:

0.0275

AC:

AN:

1198

European-Non Finnish (NFE)

AF:

0.0294

AC:

3149

AN:

107216

Other (OTH)

AF:

0.0548

AC:

624

AN:

11390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

315

631

946

1262

1577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.0789

AC:

11998

AN:

152142

Hom.:

843

Cov.:

AF XY:

0.0790

AC XY:

5875

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.184

AC:

7638

AN:

41488

American (AMR)

AF:

0.0370

AC:

565

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0470

AC:

163

AN:

3470

East Asian (EAS)

AF:

0.0880

AC:

455

AN:

5172

South Asian (SAS)

AF:

0.101

AC:

486

AN:

4822

European-Finnish (FIN)

AF:

0.0354

AC:

376

AN:

10608

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0316

AC:

2145

AN:

67974

Other (OTH)

AF:

0.0606

AC:

128

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

538

1076

1613

2151

2689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0319

Hom.:

Bravo

AF:

0.0830

Asia WGS

AF:

0.0900

AC:

312

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.74

(source)

DANN

Benign

0.65

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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