dbSNP rs6967221: RAC1:c.108-464G>A (chr7-6391460-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.108-464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 160,144 control chromosomes in the GnomAD database, including 1,024 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 0.089 ( 1005 hom., cov: 32)

Exomes 𝑓: 0.047 ( 19 hom. )

Consequence

RAC1
NM_006908.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.892

Publications

11 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5 link	c.108-464G>A		intron_variant	Intron 2 of 5	ENST00000348035.9	NP_008839.2	P63000-1A4D2P1
RAC1	NM_018890.4 link	c.108-464G>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.108-464G>A		intron_variant	Intron 2 of 5	1	NM_006908.5	ENSP00000258737.7		P63000-1

Frequencies

GnomAD3 genomes

AF:

0.0891

AC:

13539

AN:

151958

Hom.:

1001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0427

Gnomad ASJ

AF:

0.0483

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.0491

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0683

GnomAD4 exome

AF:

0.0470

AC:

379

AN:

8068

Hom.:

Cov.:

AF XY:

0.0516

AC XY:

212

AN XY:

4106

show subpopulations

African (AFR)

AF:

0.184

AC:

AN:

136

American (AMR)

AF:

0.0234

AC:

AN:

982

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

AN:

170

East Asian (EAS)

AF:

0.0842

AC:

AN:

368

South Asian (SAS)

AF:

0.130

AC:

101

AN:

776

European-Finnish (FIN)

AF:

0.0129

AC:

AN:

232

Middle Eastern (MID)

AF:

0.0417

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0339

AC:

169

AN:

4982

Other (OTH)

AF:

0.0477

AC:

AN:

398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0891

AC:

13550

AN:

152076

Hom.:

1005

Cov.:

AF XY:

0.0891

AC XY:

6625

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.195

AC:

8100

AN:

41450

American (AMR)

AF:

0.0431

AC:

658

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0483

AC:

167

AN:

3460

East Asian (EAS)

AF:

0.100

AC:

518

AN:

5158

South Asian (SAS)

AF:

0.130

AC:

628

AN:

4822

European-Finnish (FIN)

AF:

0.0491

AC:

520

AN:

10586

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0408

AC:

2774

AN:

68000

Other (OTH)

AF:

0.0676

AC:

143

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

586

1173

1759

2346

2932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0448

Hom.:

126

Bravo

AF:

0.0933

Asia WGS

AF:

0.109

AC:

381

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.69

(source)

DANN

Benign

0.66

PhyloP100

-0.89

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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rs6967221

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