chr2-20448450-G-T

Variant names:

• chr2-20448450-G-T
• rs1062292
• NM_004040.4:c.*394G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RHOB	NM_004040.4	c.*394G>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000272233.6	NP_004031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOB	ENST00000272233.6	c.*394G>T		3_prime_UTR_variant	Exon 1 of 1	6	NM_004040.4	ENSP00000272233.4

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

African (AFR) AF: 0.224 AC: 259 AN: 1156

American (AMR) AF: 0.630 AC: 1529 AN: 2428

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 560 AN: 1240

East Asian (EAS) AF: 0.867 AC: 1475 AN: 1702

South Asian (SAS) AF: 0.656 AC: 2253 AN: 3436

European-Finnish (FIN) AF: 0.488 AC: 7829 AN: 16048

Middle Eastern (MID) AF: 0.404 AC: 76 AN: 188

European-Non Finnish (NFE) AF: 0.452 AC: 11353 AN: 25122

Other (OTH) AF: 0.441 AC: 1082 AN: 2452

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

African (AFR) AF: 0.261 AC: 10840 AN: 41516

American (AMR) AF: 0.581 AC: 8891 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3472

East Asian (EAS) AF: 0.859 AC: 4443 AN: 5170

South Asian (SAS) AF: 0.693 AC: 3346 AN: 4828

European-Finnish (FIN) AF: 0.490 AC: 5185 AN: 10572

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33283 AN: 67984

Other (OTH) AF: 0.479 AC: 1012 AN: 2114

Alfa AF: 0.479 Hom.: 26300

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
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1062292; hg19: chr2-20648211;