Genetic Variant RAC1:c.107+27C>T (chr7-6387310-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006908.5(RAC1):c.107+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,442,870 control chromosomes in the GnomAD database, including 199,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 29343 hom., cov: 33)

Exomes 𝑓: 0.50 ( 170650 hom. )

Consequence

RAC1
NM_006908.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.769

Publications

16 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 7-6387310-C-T is Benign according to our data. Variant chr7-6387310-C-T is described in ClinVar as [Benign]. Clinvar id is 1327929.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5 link	c.107+27C>T		intron_variant	Intron 2 of 5	ENST00000348035.9	NP_008839.2	P63000-1A4D2P1
RAC1	NM_018890.4 link	c.107+27C>T		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.107+27C>T		intron_variant	Intron 2 of 5	1	NM_006908.5	ENSP00000258737.7		P63000-1

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90919

AN:

151976

Hom.:

29276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.814

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.909

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.559

GnomAD2 exomes

AF:

0.543

AC:

112942

AN:

207992

AF XY:

0.532

show subpopulations

Gnomad AFR exome

AF:

0.812

Gnomad AMR exome

AF:

0.674

Gnomad ASJ exome

AF:

0.369

Gnomad EAS exome

AF:

0.903

Gnomad FIN exome

AF:

0.473

Gnomad NFE exome

AF:

0.447

Gnomad OTH exome

AF:

0.491

GnomAD4 exome

AF:

0.503

AC:

649201

AN:

1290776

Hom.:

170650

Cov.:

AF XY:

0.503

AC XY:

326689

AN XY:

648906

show subpopulations

African (AFR)

AF:

0.818

AC:

22186

AN:

27114

American (AMR)

AF:

0.669

AC:

21132

AN:

31564

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

9162

AN:

24094

East Asian (EAS)

AF:

0.904

AC:

32675

AN:

36146

South Asian (SAS)

AF:

0.610

AC:

46086

AN:

75546

European-Finnish (FIN)

AF:

0.471

AC:

24828

AN:

52740

Middle Eastern (MID)

AF:

0.452

AC:

2444

AN:

5412

European-Non Finnish (NFE)

AF:

0.469

AC:

461377

AN:

983564

Other (OTH)

AF:

0.537

AC:

29311

AN:

54596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

13075

26150

39226

52301

65376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.599

AC:

91048

AN:

152094

Hom.:

29343

Cov.:

AF XY:

0.602

AC XY:

44764

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.814

AC:

33815

AN:

41518

American (AMR)

AF:

0.636

AC:

9701

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1298

AN:

3472

East Asian (EAS)

AF:

0.909

AC:

4712

AN:

5184

South Asian (SAS)

AF:

0.639

AC:

3084

AN:

4826

European-Finnish (FIN)

AF:

0.475

AC:

5011

AN:

10554

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.466

AC:

31649

AN:

67970

Other (OTH)

AF:

0.565

AC:

1192

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1721

3443

5164

6886

8607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.508

Hom.:

3920

Bravo

AF:

0.621

Asia WGS

AF:

0.816

AC:

2834

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 48

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.0

(source)

DANN

Benign

0.57

PhyloP100

0.77

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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7-6387310-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over