rs2177268

Positions:

• chr3-49402292-A-T

Variant summary

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

The NM_001664.4(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 NM_001664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOA	NM_001664.4	c.-3+9528T>A		intron_variant		ENST00000418115.6	NP_001655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6	c.-3+9528T>A		intron_variant		1	NM_001664.4	ENSP00000400175	P1

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

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.00848

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.246

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.33

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: rs2177268; hg19: chr3-49439725;