dbSNP rs9374: RAC1:c.*294G>A (chr7-6402740-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_006908.5(RAC1):c.*294G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 269,590 control chromosomes in the GnomAD database, including 5,233 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 0.18 ( 2801 hom., cov: 31)

Exomes 𝑓: 0.19 ( 2432 hom. )

Consequence

RAC1
NM_006908.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.42

Publications

26 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5 link	c.*294G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000348035.9	NP_008839.2	P63000-1A4D2P1
RAC1	NM_018890.4 link	c.*294G>A		3_prime_UTR_variant	Exon 7 of 7		NP_061485.1	P63000-2A4D2P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9 link	c.*294G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_006908.5	ENSP00000258737.7		P63000-1

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26870

AN:

151722

Hom.:

2800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0731

Gnomad AMI

AF:

0.0870

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.0994

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.162

GnomAD4 exome

AF:

0.190

AC:

22329

AN:

117748

Hom.:

2432

Cov.:

AF XY:

0.186

AC XY:

11008

AN XY:

59096

show subpopulations

African (AFR)

AF:

0.0702

AC:

285

AN:

4062

American (AMR)

AF:

0.156

AC:

741

AN:

4764

Ashkenazi Jewish (ASJ)

AF:

0.0925

AC:

512

AN:

5536

East Asian (EAS)

AF:

0.202

AC:

2194

AN:

10886

South Asian (SAS)

AF:

0.127

AC:

961

AN:

7590

European-Finnish (FIN)

AF:

0.215

AC:

662

AN:

3082

Middle Eastern (MID)

AF:

0.117

AC:

AN:

598

European-Non Finnish (NFE)

AF:

0.211

AC:

15424

AN:

73182

Other (OTH)

AF:

0.184

AC:

1480

AN:

8048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

837

1674

2512

3349

4186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.177

AC:

26875

AN:

151842

Hom.:

2801

Cov.:

AF XY:

0.176

AC XY:

13070

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.0730

AC:

3024

AN:

41444

American (AMR)

AF:

0.156

AC:

2381

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.0994

AC:

345

AN:

3470

East Asian (EAS)

AF:

0.232

AC:

1191

AN:

5140

South Asian (SAS)

AF:

0.150

AC:

722

AN:

4806

European-Finnish (FIN)

AF:

0.265

AC:

2783

AN:

10486

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.235

AC:

15971

AN:

67944

Other (OTH)

AF:

0.163

AC:

343

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1026

2052

3077

4103

5129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.210

Hom.:

5087

Bravo

AF:

0.169

Asia WGS

AF:

0.199

AC:

691

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

2.4

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)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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