3-49368647-T-C

Position:

• chr3-49368647-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001664.4(RHOA):​c.157-99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,272,802 control chromosomes in the GnomAD database, including 145,747 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 0.44 (15783 hom., cov: 30)
  • Exomes 𝑓: 0.46 (129964 hom.)
• Consequence: RHOA NM_001664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

ENSG00000290318 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOA	NM_001664.4	c.157-99A>G		intron_variant		ENST00000418115.6	NP_001655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6	c.157-99A>G		intron_variant		1	NM_001664.4	ENSP00000400175.1
ENSG00000290318	ENST00000704381.1	c.157-99A>G		intron_variant				ENSP00000515884.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66237 AN: 151646 Hom.: 15772 Cov.: 30

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.462 AC: 518255 AN: 1121042 Hom.: 129964 AF XY: 0.469 AC XY: 266662 AN XY: 568878

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.693

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.934

Gnomad4 SAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.437 AC: 66282 AN: 151760 Hom.: 15783 Cov.: 30 AF XY: 0.443 AC XY: 32820 AN XY: 74144

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.440

Alfa AF: 0.430 Hom.: 2893

Bravo AF: 0.452

Asia WGS AF: 0.776 AC: 2692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.9
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs2878298; hg19: chr3-49406080;