rs4952834

Positions:

• chr2-46550323-G-C

Variant summary

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

The NM_012249.4(RHOQ):​c.201+6511G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,034 control chromosomes in the GnomAD database, including 6,589 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 0.29 (6589 hom., cov: 32)
• Consequence: RHOQ NM_012249.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOQ	NM_012249.4	c.201+6511G>C		intron_variant		ENST00000238738.9	NP_036381.2
RHOQ	XM_011532726.3	c.201+6511G>C		intron_variant			XP_011531028.1
RHOQ	XM_005264229.3	c.201+6511G>C		intron_variant			XP_005264286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOQ	ENST00000238738.9	c.201+6511G>C		intron_variant		1	NM_012249.4	ENSP00000238738.4

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44048 AN: 151922 Hom.: 6569 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.290 AC: 44098 AN: 152034 Hom.: 6589 Cov.: 32 AF XY: 0.288 AC XY: 21401 AN XY: 74292

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.279

Alfa AF: 0.323 Hom.: 952

Bravo AF: 0.292

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.60

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: rs4952834; hg19: chr2-46777462;