rs3448

Positions:

• chr3-49359318-T-C
• chr3-49359318-T-G

Variant summary

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

The NM_001664.4(RHOA):​c.*891A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 191,826 control chromosomes in the GnomAD database, including 57,056 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 0.76 (44441 hom., cov: 30)
  • Exomes 𝑓: 0.79 (12615 hom.)
• Consequence: RHOA NM_001664.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOA	NM_001664.4	c.*891A>G		3_prime_UTR_variant	5/5	ENST00000418115.6	NP_001655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115	c.*891A>G		3_prime_UTR_variant	5/5	1	NM_001664.4	ENSP00000400175.1
ENSG00000290318	ENST00000704381.1	c.464+1009A>G		intron_variant				ENSP00000515884.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115777 AN: 151918 Hom.: 44412 Cov.: 30

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.751

GnomAD4 exome AF: 0.788 AC: 31368 AN: 39790 Hom.: 12615 Cov.: 0 AF XY: 0.789 AC XY: 14628 AN XY: 18532

Gnomad4 AFR exome AF: 0.722

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.952

Gnomad4 FIN exome AF: 0.771

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.754

GnomAD4 genome AF: 0.762 AC: 115852 AN: 152036 Hom.: 44441 Cov.: 30 AF XY: 0.770 AC XY: 57194 AN XY: 74304

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.754

Alfa AF: 0.745 Hom.: 86004

Bravo AF: 0.759

Asia WGS AF: 0.933 AC: 3244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3448; hg19: chr3-49396751;