Variant chr3-49375563-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001664.4(RHOA):c.27G>A(p.Val9Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,613,688 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

RHOA
NM_001664.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.382

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 links:

ENSG00000290318 (HGNC:):

ENSG00000290318 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 3-49375563-C-T is Benign according to our data. Variant chr3-49375563-C-T is described in ClinVar as [Benign]. Clinvar id is 720567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.382 with no splicing effect.

BS2

High AC in GnomAd4 at 383 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOA	NM_001664.4 linkuse as main transcript	c.27G>A	p.Val9Val	synonymous_variant	2/5	ENST00000418115.6	NP_001655.1	P61586A0A024R324Q9BVT0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6 linkuse as main transcript	c.27G>A	p.Val9Val	synonymous_variant	2/5	1	NM_001664.4	ENSP00000400175.1		P61586
ENSG00000290318	ENST00000704381.1 linkuse as main transcript	c.27G>A	p.Val9Val	synonymous_variant	2/6			ENSP00000515884.1		A0A994J514

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

382

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000737

AC:

185

AN:

250848

Hom.:

AF XY:

0.000649

AC XY:

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00960

Gnomad AMR exome

AF:

0.000495

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000263

AC:

385

AN:

1461384

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

182

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.00846

Gnomad4 AMR exome

AF:

0.000583

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.00251

AC:

383

AN:

152304

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00868

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00309

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.3

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over