rs1987628

Positions:

• chr3-49361826-G-A

Variant summary

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

The NM_001664.4(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 NM_001664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHOA	NM_001664.4	c.408+670C>T		intron_variant		ENST00000418115.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOA	ENST00000418115.6	c.408+670C>T		intron_variant		1	NM_001664.4	P1

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

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.0591

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.286

Alfa AF: 0.287 Hom.: 816

Bravo AF: 0.258

Asia WGS AF: 0.141 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.32

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: rs1987628; hg19: chr3-49399259;