rs1062292

chr2-20448450-G-T

Variant summary

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

The NM_004040.4(RHOB):c.*394G>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 0.465 in 205,932 control chromosomes in the GnomAD database, including 24,476 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 0.46 (17429 hom., cov: 34)
  • Exomes 𝑓: 0.49 (7047 hom.)
• Consequence: RHOB NM_004040.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

Genes affected

RHOB (HGNC:668): (ras homolog family member B) Predicted to enable GTP binding activity; GTPase activity; and protein kinase binding activity. Involved in several processes, including cellular response to hydrogen peroxide; cellular response to ionizing radiation; and regulation of cell migration. Located in cleavage furrow and endosome membrane. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHOB	NM_004040.4	c.*394G>T		3_prime_UTR_variant	1/1	ENST00000272233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOB	ENST00000272233.6	c.*394G>T		3_prime_UTR_variant	1/1		NM_004040.4	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69236 AN: 152042 Hom.: 17408 Cov.: 34

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.491 AC: 26416 AN: 53772 Hom.: 7047 Cov.: 0 AF XY: 0.496 AC XY: 13446 AN XY: 27102

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.867

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.488

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.455 AC: 69286 AN: 152160 Hom.: 17429 Cov.: 34 AF XY: 0.464 AC XY: 34531 AN XY: 74392

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.479

Alfa AF: 0.480 Hom.: 17789

Bravo AF: 0.453

Asia WGS AF: 0.726 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	14
Dann	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1062292; hg19: chr2-20648211;