rs1987628

Variant names:

• chr3-49361826-G-A
• rs1987628
• NM_001664.4:c.408+670C>T

Variant summary

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

The ENST00000418115.6(RHOA):​c.408+670C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,876 control chromosomes in the GnomAD database, including 6,549 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 0.28 (6549 hom., cov: 32)
• Consequence: RHOA ENST00000418115.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 27 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 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.408+670C>T		intron	N/A	NP_001655.1
	RHOA	NM_001313941.2		c.408+670C>T		intron	N/A	NP_001300870.1
	RHOA	NM_001313943.2		c.408+670C>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.408+670C>T		intron	N/A	ENSP00000400175.1
	ENSG00000290318	ENST00000704381.1		c.408+670C>T		intron	N/A	ENSP00000515884.1
	RHOA	ENST00000678921.2		c.*664C>T		3_prime_UTR	Exon 4 of 4	ENSP00000503490.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42636 AN: 151758 Hom.: 6547 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.281 AC: 42651 AN: 151876 Hom.: 6549 Cov.: 32 AF XY: 0.284 AC XY: 21065 AN XY: 74212

African (AFR) AF: 0.235 AC: 9716 AN: 41412

American (AMR) AF: 0.216 AC: 3283 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1600 AN: 3470

East Asian (EAS) AF: 0.0591 AC: 306 AN: 5176

South Asian (SAS) AF: 0.227 AC: 1093 AN: 4814

European-Finnish (FIN) AF: 0.472 AC: 4973 AN: 10530

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20805 AN: 67942

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.286 Hom.: 845

Bravo AF: 0.258

Asia WGS AF: 0.141 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.32
PhyloP100		0.49
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: rs1987628; hg19: chr3-49399259;