rs3448

Variant names:

• chr3-49359318-T-C
• rs3448
• NM_001664.4:c.*891A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 85 publications found

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 Gene-Disease associations (from GenCC):

• ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000290318 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RHOA	NM_001664.4	c.*891A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000418115.6	NP_001655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6	c.*891A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_001664.4	ENSP00000400175.1
ENSG00000290318	ENST00000704381.1	c.464+1009A>G		intron_variant	Intron 5 of 5			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

African (AFR) AF: 0.722 AC: 1073 AN: 1486

American (AMR) AF: 0.825 AC: 846 AN: 1026

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2062 AN: 2586

East Asian (EAS) AF: 0.999 AC: 6886 AN: 6890

South Asian (SAS) AF: 0.952 AC: 299 AN: 314

European-Finnish (FIN) AF: 0.771 AC: 356 AN: 462

Middle Eastern (MID) AF: 0.740 AC: 179 AN: 242

European-Non Finnish (NFE) AF: 0.732 AC: 17220 AN: 23540

Other (OTH) AF: 0.754 AC: 2447 AN: 3244

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

African (AFR) AF: 0.730 AC: 30256 AN: 41444

American (AMR) AF: 0.808 AC: 12324 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2807 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5127 AN: 5172

South Asian (SAS) AF: 0.914 AC: 4409 AN: 4824

European-Finnish (FIN) AF: 0.818 AC: 8656 AN: 10580

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49805 AN: 67968

Other (OTH) AF: 0.754 AC: 1595 AN: 2116

Alfa AF: 0.746 Hom.: 179341

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
PhyloP100		-0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3448; hg19: chr3-49396751;