chr3-49358927-T-C

Variant names:

• chr3-49358927-T-C
• rs3811699
• ENST00000704381.1:c.465-1180A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000704381.1(ENSG00000290318):​c.465-1180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,910 control chromosomes in the GnomAD database, including 7,203 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 0.30 (7203 hom., cov: 31)
• Consequence: ENSG00000290318 ENST00000704381.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 57 publications found

Genes affected

ENSG00000290318 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000704381.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOA	NM_001664.4	MANE Select	c.*1282A>G		downstream_gene	N/A	NP_001655.1
	RHOA	NM_001313941.2		c.*1282A>G		downstream_gene	N/A	NP_001300870.1
	RHOA	NM_001313943.2		c.*1439A>G		downstream_gene	N/A	NP_001300872.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290318	ENST00000704381.1		c.465-1180A>G		intron	N/A	ENSP00000515884.1
	ENSG00000290318	ENST00000704379.1		n.14A>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000290318	ENST00000704380.1		n.85+130A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45157 AN: 151792 Hom.: 7196 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.0628

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45186 AN: 151910 Hom.: 7203 Cov.: 31 AF XY: 0.300 AC XY: 22244 AN XY: 74252

African (AFR) AF: 0.293 AC: 12129 AN: 41430

American (AMR) AF: 0.219 AC: 3347 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1600 AN: 3470

East Asian (EAS) AF: 0.0631 AC: 326 AN: 5166

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4810

European-Finnish (FIN) AF: 0.473 AC: 4972 AN: 10522

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20818 AN: 67938

Other (OTH) AF: 0.297 AC: 628 AN: 2112

Alfa AF: 0.295 Hom.: 5965

Bravo AF: 0.278

Asia WGS AF: 0.152 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.66
DANN	Benign	0.64
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs3811699; hg19: chr3-49396360;