dbSNP rs6951997: RAC1:c.*931T>G (chr7-6403377-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006908.5(RAC1):c.*931T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 212,312 control chromosomes in the GnomAD database, including 73 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 0.020 ( 66 hom., cov: 33)

Exomes 𝑓: 0.011 ( 7 hom. )

Consequence

RAC1
NM_006908.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.807

Publications

7 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=-0.74).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0195 (2975/152320) while in subpopulation AFR AF = 0.0438 (1820/41540). AF 95% confidence interval is 0.0421. There are 66 homozygotes in GnomAd4. There are 1465 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2975 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5 link	c.*931T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000348035.9	NP_008839.2	P63000-1A4D2P1
RAC1	NM_018890.4 link	c.*931T>G		3_prime_UTR_variant	Exon 7 of 7		NP_061485.1	P63000-2A4D2P0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAC1	ENST00000348035.9 link	c.*931T>G	3_prime_UTR_variant	Exon 6 of 6	1	NM_006908.5	ENSP00000258737.7	P63000-1
RAC1	ENST00000704003.1 link	n.*1463T>G	non_coding_transcript_exon_variant	Exon 7 of 7			ENSP00000515616.1	A0A994J4S4
RAC1	ENST00000704003.1 link	n.*1463T>G	3_prime_UTR_variant	Exon 7 of 7			ENSP00000515616.1	A0A994J4S4

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2972

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0438

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0138

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00942

Gnomad OTH

AF:

0.0124

GnomAD4 exome

AF:

0.0112

AC:

673

AN:

59992

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

318

AN XY:

27792

show subpopulations

African (AFR)

AF:

0.0450

AC:

120

AN:

2666

American (AMR)

AF:

0.00854

AC:

AN:

1756

Ashkenazi Jewish (ASJ)

AF:

0.00131

AC:

AN:

3822

East Asian (EAS)

AF:

0.00702

AC:

AN:

8834

South Asian (SAS)

AF:

0.0227

AC:

AN:

528

European-Finnish (FIN)

AF:

0.0107

AC:

AN:

468

Middle Eastern (MID)

AF:

0.00824

AC:

AN:

364

European-Non Finnish (NFE)

AF:

0.0103

AC:

378

AN:

36626

Other (OTH)

AF:

0.0148

AC:

AN:

4928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

107

143

179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0195

AC:

2975

AN:

152320

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1465

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0438

AC:

1820

AN:

41540

American (AMR)

AF:

0.00830

AC:

127

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.0139

AC:

AN:

5192

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4830

European-Finnish (FIN)

AF:

0.0135

AC:

143

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00942

AC:

641

AN:

68034

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

135

270

406

541

676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0198

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.0

(source)

DANN

Benign

0.72

PhyloP100

0.81

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