2-46570866-C-G

Position:

• chr2-46570866-C-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOQ	NM_012249.4	c.202-5221C>G		intron_variant		ENST00000238738.9	NP_036381.2
RHOQ	XM_011532726.3	c.202-5221C>G		intron_variant			XP_011531028.1
RHOQ	XM_005264229.3	c.202-10062C>G		intron_variant			XP_005264286.1
RHOQ-AS1	NR_104182.1	n.205-1296G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOQ	ENST00000238738.9	c.202-5221C>G		intron_variant		1	NM_012249.4	ENSP00000238738.4

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

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.388

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.4
DANN	Benign	0.70

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: rs13420857; hg19: chr2-46798005;