chr3-49402292-A-T

Variant names:

• chr3-49402292-A-T
• rs2177268
• NM_001664.4:c.-3+9528T>A

Variant summary

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

The ENST00000418115.6(RHOA):​c.-3+9528T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,038 control chromosomes in the GnomAD database, including 4,604 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 0.24 (4604 hom., cov: 32)
• Consequence: RHOA ENST00000418115.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 14 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418115.6. 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.-3+9528T>A		intron	N/A	NP_001655.1
	RHOA	NM_001313941.2		c.-3+4420T>A		intron	N/A	NP_001300870.1
	RHOA	NM_001313943.2		c.-3+9528T>A		intron	N/A	NP_001300872.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOA	ENST00000418115.6	TSL:1 MANE Select	c.-3+9528T>A		intron	N/A	ENSP00000400175.1
	ENSG00000290318	ENST00000704381.1		c.-3+9528T>A		intron	N/A	ENSP00000515884.1
	RHOA	ENST00000445425.6	TSL:3	c.-3+4420T>A		intron	N/A	ENSP00000408402.3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36122 AN: 151920 Hom.: 4591 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.00865

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.238 AC: 36165 AN: 152038 Hom.: 4604 Cov.: 32 AF XY: 0.230 AC XY: 17094 AN XY: 74328

African (AFR) AF: 0.269 AC: 11179 AN: 41484

American (AMR) AF: 0.192 AC: 2921 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 664 AN: 3466

East Asian (EAS) AF: 0.00848 AC: 44 AN: 5188

South Asian (SAS) AF: 0.0860 AC: 415 AN: 4826

European-Finnish (FIN) AF: 0.181 AC: 1913 AN: 10556

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18179 AN: 67954

Other (OTH) AF: 0.246 AC: 521 AN: 2114

Alfa AF: 0.251 Hom.: 606

Bravo AF: 0.241

Asia WGS AF: 0.0660 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.33
PhyloP100		0.056
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: rs2177268; hg19: chr3-49439725;