rs585017

Variant names:

• chr2-20446871-G-A
• rs585017
• ENST00000702995.2:n.38C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-20446871-G-A
• chr2-20446871-G-C
• chr2-20446871-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000702995.2(ENSG00000290108):​n.38C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 151,996 control chromosomes in the GnomAD database, including 44,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (44520 hom., cov: 33)
• Consequence: ENSG00000290108 ENST00000702995.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.202
• Publications: 5 publications found

Genes affected

ENSG00000290108 (HGNC:):

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-20446871-G-A is Benign according to our data. Variant chr2-20446871-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000702995.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOB	NM_004040.4	MANE Select	c.-595G>A		upstream_gene	N/A	NP_004031.1	P62745

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290108	ENST00000702995.2		n.38C>T		non_coding_transcript_exon	Exon 1 of 1
	RHOB	ENST00000272233.6	TSL:6 MANE Select	c.-595G>A		upstream_gene	N/A	ENSP00000272233.4	P62745

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116005 AN: 151878 Hom.: 44463 Cov.: 33

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.764 AC: 116123 AN: 151996 Hom.: 44520 Cov.: 33 AF XY: 0.769 AC XY: 57126 AN XY: 74288

African (AFR) AF: 0.797 AC: 33056 AN: 41484

American (AMR) AF: 0.809 AC: 12328 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2407 AN: 3466

East Asian (EAS) AF: 0.920 AC: 4691 AN: 5100

South Asian (SAS) AF: 0.812 AC: 3918 AN: 4826

European-Finnish (FIN) AF: 0.751 AC: 7964 AN: 10598

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49344 AN: 67962

Other (OTH) AF: 0.766 AC: 1621 AN: 2116

Alfa AF: 0.651 Hom.: 1809

Bravo AF: 0.770

Asia WGS AF: 0.860 AC: 2988 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.2
DANN	Benign	0.95
PhyloP100		-0.20
PromoterAI		0.051	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs585017;

hg19: chr2-20646632;