rs17595772

Positions:

• chr3-49372271-G-A
• chr3-49372271-G-C

Variant summary

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

The NM_001664.4(RHOA):​c.156+3163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,998 control chromosomes in the GnomAD database, including 15,832 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 (15832 hom., cov: 31)
• Consequence: RHOA NM_001664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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=-0.88).
• 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.156+3163C>T		intron_variant		ENST00000418115.6	NP_001655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6	c.156+3163C>T		intron_variant		1	NM_001664.4	ENSP00000400175	P1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66398 AN: 151880 Hom.: 15821 Cov.: 31

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.437 AC: 66442 AN: 151998 Hom.: 15832 Cov.: 31 AF XY: 0.443 AC XY: 32893 AN XY: 74274

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.440

Alfa AF: 0.427 Hom.: 3322

Bravo AF: 0.452

Asia WGS AF: 0.777 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.30

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: rs17595772; hg19: chr3-49409704;