dbSNP rs8179164: RHOA:c.*358A>T (chr3-49359851-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001664.4(RHOA):c.*358A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 261,440 control chromosomes in the GnomAD database, including 74 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 ( 39 hom., cov: 32)

Exomes 𝑓: 0.021 ( 35 hom. )

Consequence

RHOA
NM_001664.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.408

Publications

15 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0204 (3100/152278) while in subpopulation NFE AF = 0.0307 (2086/68024). AF 95% confidence interval is 0.0296. There are 39 homozygotes in GnomAd4. There are 1569 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOA	NM_001664.4 link	c.*358A>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000418115.6	NP_001655.1	P61586A0A024R324Q9BVT0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6 link	c.*358A>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001664.4	ENSP00000400175.1		P61586
ENSG00000290318	ENST00000704381.1 link	c.464+476A>T		intron_variant	Intron 5 of 5			ENSP00000515884.1		A0A994J514

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3100

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0515

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0143

GnomAD4 exome

AF:

0.0205

AC:

2242

AN:

109162

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1028

AN XY:

52624

show subpopulations

African (AFR)

AF:

0.00454

AC:

AN:

4408

American (AMR)

AF:

0.0129

AC:

AN:

4114

Ashkenazi Jewish (ASJ)

AF:

0.00159

AC:

AN:

5674

East Asian (EAS)

AF:

0.00

AC:

AN:

12040

South Asian (SAS)

AF:

0.000239

AC:

AN:

4176

European-Finnish (FIN)

AF:

0.0534

AC:

151

AN:

2830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

590

European-Non Finnish (NFE)

AF:

0.0273

AC:

1833

AN:

67166

Other (OTH)

AF:

0.0214

AC:

175

AN:

8164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

112

224

335

447

559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0204

AC:

3100

AN:

152278

Hom.:

Cov.:

AF XY:

0.0211

AC XY:

1569

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00483

AC:

201

AN:

41576

American (AMR)

AF:

0.0145

AC:

222

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0515

AC:

545

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0307

AC:

2086

AN:

68024

Other (OTH)

AF:

0.0142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

151

301

452

602

753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0248

Hom.:

Bravo

AF:

0.0164

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.9

(source)

DANN

Benign

0.82

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism

(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