rs8179164

Positions:

• chr3-49359851-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000418115.6(RHOA):​c.*358A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 261,440 control chromosomes in the GnomAD database, including 74 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 0.020 (39 hom., cov: 32)
  • Exomes 𝑓: 0.021 (35 hom.)
• Consequence: RHOA ENST00000418115.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

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=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0204 (3100/152278) while in subpopulation NFE AF= 0.0307 (2086/68024). AF 95% confidence interval is 0.0296. There are 39 homozygotes in gnomad4. There are 1569 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOA	NM_001664.4	c.*358A>T		3_prime_UTR_variant	5/5	ENST00000418115.6	NP_001655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOA	ENST00000418115.6	c.*358A>T		3_prime_UTR_variant	5/5	1	NM_001664.4	ENSP00000400175	P1

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3100 AN: 152160 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.0205 AC: 2242 AN: 109162 Hom.: 35 Cov.: 0 AF XY: 0.0195 AC XY: 1028 AN XY: 52624

Gnomad4 AFR exome AF: 0.00454

Gnomad4 AMR exome AF: 0.0129

Gnomad4 ASJ exome AF: 0.00159

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000239

Gnomad4 FIN exome AF: 0.0534

Gnomad4 NFE exome AF: 0.0273

Gnomad4 OTH exome AF: 0.0214

GnomAD4 genome AF: 0.0204 AC: 3100 AN: 152278 Hom.: 39 Cov.: 32 AF XY: 0.0211 AC XY: 1569 AN XY: 74460

Gnomad4 AFR AF: 0.00483

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0248 Hom.: 4

Bravo AF: 0.0164

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.9
DANN	Benign	0.82

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: rs8179164; hg19: chr3-49397284;