Genetic Variant RHOA:c.157-114C>T (chr3-49368662-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001664.4(RHOA):c.157-114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,080,842 control chromosomes in the GnomAD database, including 3,510 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 0.061 ( 401 hom., cov: 31)

Exomes 𝑓: 0.074 ( 3109 hom. )

Consequence

RHOA
NM_001664.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.205

Publications

23 publications found

Variant links:

Genes affected

RHOA (HGNC:667): (ras homolog family member A) This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]

RHOA Gene-Disease associations (from GenCC):

ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

RHOA links:

ENSG00000290318 (HGNC:):

ENSG00000290318 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOA	NM_001664.4 link	c.157-114C>T		intron_variant	Intron 2 of 4	ENST00000418115.6	NP_001655.1	P61586A0A024R324Q9BVT0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6 link	c.157-114C>T		intron_variant	Intron 2 of 4	1	NM_001664.4	ENSP00000400175.1		P61586
ENSG00000290318	ENST00000704381.1 link	c.157-114C>T		intron_variant	Intron 2 of 5			ENSP00000515884.1		A0A994J514

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9175

AN:

151398

Hom.:

401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0169

Gnomad AMI

AF:

0.0872

Gnomad AMR

AF:

0.0527

Gnomad ASJ

AF:

0.0896

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.0953

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0889

Gnomad OTH

AF:

0.0589

GnomAD4 exome

AF:

0.0745

AC:

69194

AN:

929342

Hom.:

3109

AF XY:

0.0731

AC XY:

34955

AN XY:

478010

show subpopulations

African (AFR)

AF:

0.0138

AC:

295

AN:

21386

American (AMR)

AF:

0.0419

AC:

1242

AN:

29618

Ashkenazi Jewish (ASJ)

AF:

0.0853

AC:

1718

AN:

20138

East Asian (EAS)

AF:

0.000110

AC:

AN:

36456

South Asian (SAS)

AF:

0.0219

AC:

1483

AN:

67632

European-Finnish (FIN)

AF:

0.0943

AC:

4732

AN:

50156

Middle Eastern (MID)

AF:

0.0383

AC:

175

AN:

4570

European-Non Finnish (NFE)

AF:

0.0862

AC:

56656

AN:

657298

Other (OTH)

AF:

0.0686

AC:

2889

AN:

42088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

3019

6039

9058

12078

15097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1478

2956

4434

5912

7390

<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:

0.0605

AC:

9171

AN:

151500

Hom.:

401

Cov.:

AF XY:

0.0601

AC XY:

4445

AN XY:

73998

show subpopulations

African (AFR)

AF:

0.0169

AC:

697

AN:

41316

American (AMR)

AF:

0.0527

AC:

800

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

311

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0240

AC:

115

AN:

4794

European-Finnish (FIN)

AF:

0.0953

AC:

993

AN:

10416

Middle Eastern (MID)

AF:

0.0719

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0889

AC:

6032

AN:

67854

Other (OTH)

AF:

0.0578

AC:

121

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

432

865

1297

1730

2162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0748

Hom.:

942

Bravo

AF:

0.0558

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.32

Position offset: 1

DS_DG_spliceai

0.27

Position offset: -40

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