2-46570866-C-G

Variant names:

• chr2-46570866-C-G
• rs13420857
• NM_012249.4:c.202-5221C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012249.4(RHOQ):​c.202-5221C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,068 control chromosomes in the GnomAD database, including 13,989 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 0.41 (13989 hom., cov: 32)
• Consequence: RHOQ NM_012249.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 9 publications found

Genes affected

RHOQ (HGNC:17736): (ras homolog family member Q) 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. The encoded protein is an important signalling protein for sarcomere assembly and has been shown to play a significant role in the exocytosis of the solute carrier family 2, facilitated glucose transporter member 4 and other proteins, possibly acting as the signal that turns on the membrane fusion machinery. Three related pseudogene have been identified on chromosomes 2 and 14. [provided by RefSeq, Aug 2011]

RHOQ-AS1 (HGNC:40816): (RHOQ antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012249.4. 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
	RHOQ	NM_012249.4	MANE Select	c.202-5221C>G		intron	N/A	NP_036381.2	P17081
	RHOQ-AS1	NR_104182.1		n.205-1296G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOQ	ENST00000238738.9	TSL:1 MANE Select	c.202-5221C>G		intron	N/A	ENSP00000238738.4	P17081
	RHOQ-AS1	ENST00000506009.3	TSL:1	n.215-1296G>C		intron	N/A
	RHOQ	ENST00000945010.1		c.143-5300C>G		intron	N/A	ENSP00000615069.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62906 AN: 151950 Hom.: 13961 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.414 AC: 62976 AN: 152068 Hom.: 13989 Cov.: 32 AF XY: 0.407 AC XY: 30265 AN XY: 74342

African (AFR) AF: 0.564 AC: 23380 AN: 41444

American (AMR) AF: 0.418 AC: 6394 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1518 AN: 3470

East Asian (EAS) AF: 0.140 AC: 724 AN: 5178

South Asian (SAS) AF: 0.367 AC: 1771 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2880 AN: 10578

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.368 AC: 25013 AN: 67966

Other (OTH) AF: 0.388 AC: 821 AN: 2114

Alfa AF: 0.257 Hom.: 569

Bravo AF: 0.429

Asia WGS AF: 0.281 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.4
DANN	Benign	0.70
PhyloP100		-0.013
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: rs13420857; hg19: chr2-46798005;