rs8179164

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

2

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

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
RHOANM_001664.4 linkc.*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
RHOAENST00000418115.6 linkc.*358A>T 3_prime_UTR_variant Exon 5 of 5 1 NM_001664.4 ENSP00000400175.1 P61586
ENSG00000290318ENST00000704381.1 linkc.464+476A>T intron_variant Intron 5 of 5 ENSP00000515884.1 A0A994J514

Frequencies

GnomAD3 genomes
AF:
0.0204
AC:
3100
AN:
152160
Hom.:
39
Cov.:
32
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.:
35
Cov.:
0
AF XY:
0.0195
AC XY:
1028
AN XY:
52624
show subpopulations
African (AFR)
AF:
0.00454
AC:
20
AN:
4408
American (AMR)
AF:
0.0129
AC:
53
AN:
4114
Ashkenazi Jewish (ASJ)
AF:
0.00159
AC:
9
AN:
5674
East Asian (EAS)
AF:
0.00
AC:
0
AN:
12040
South Asian (SAS)
AF:
0.000239
AC:
1
AN:
4176
European-Finnish (FIN)
AF:
0.0534
AC:
151
AN:
2830
Middle Eastern (MID)
AF:
0.00
AC:
0
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
0
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
0
10
20
30
40
50
<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.:
39
Cov.:
32
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:
11
AN:
3472
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5186
South Asian (SAS)
AF:
0.000829
AC:
4
AN:
4828
European-Finnish (FIN)
AF:
0.0515
AC:
545
AN:
10592
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0307
AC:
2086
AN:
68024
Other (OTH)
AF:
0.0142
AC:
30
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
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
0
42
84
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.:
4
Bravo
AF:
0.0164
Asia WGS
AF:
0.00202
AC:
7
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
DANN
Benign
0.82
PhyloP100
0.41
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs8179164; hg19: chr3-49397284; API