rs17595772

Variant names:

• chr3-49372271-G-A
• rs17595772
• NM_001664.4:c.156+3163C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001664.4. 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.156+3163C>T		intron	N/A	NP_001655.1
	RHOA	NM_001313941.2		c.156+3163C>T		intron	N/A	NP_001300870.1
	RHOA	NM_001313943.2		c.156+3163C>T		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.156+3163C>T		intron	N/A	ENSP00000400175.1
	ENSG00000290318	ENST00000704381.1		c.156+3163C>T		intron	N/A	ENSP00000515884.1
	RHOA	ENST00000445425.6	TSL:3	c.156+3163C>T		intron	N/A	ENSP00000408402.3

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

African (AFR) AF: 0.343 AC: 14212 AN: 41462

American (AMR) AF: 0.578 AC: 8825 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3470

East Asian (EAS) AF: 0.930 AC: 4806 AN: 5168

South Asian (SAS) AF: 0.686 AC: 3300 AN: 4810

European-Finnish (FIN) AF: 0.346 AC: 3643 AN: 10544

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28928 AN: 67974

Other (OTH) AF: 0.440 AC: 928 AN: 2110

Alfa AF: 0.426 Hom.: 5386

Bravo AF: 0.452

Asia WGS AF: 0.777 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.30
PhyloP100		0.15
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: rs17595772; hg19: chr3-49409704;