chr3-49358927-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOA	NM_001664.4	c.*1282A>G		downstream_gene_variant		ENST00000418115.6	NP_001655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290318	ENST00000704381.1	c.465-1180A>G		intron_variant	Intron 5 of 5			ENSP00000515884.1
RHOA	ENST00000418115.6	c.*1282A>G		downstream_gene_variant		1	NM_001664.4	ENSP00000400175.1

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

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.0631

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.297

Alfa AF: 0.296 Hom.: 4266

Bravo AF: 0.278

Asia WGS AF: 0.152 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3811699; hg19: chr3-49396360;