NM_012249.4:c.201+6511G>C

Variant names:

• chr2-46550323-G-C
• rs4952834
• NM_012249.4:c.201+6511G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.201+6511G>C		intron	N/A	NP_036381.2	P17081

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOQ	ENST00000238738.9	TSL:1 MANE Select	c.201+6511G>C		intron	N/A	ENSP00000238738.4	P17081
	RHOQ	ENST00000945010.1		c.142+7135G>C		intron	N/A	ENSP00000615069.1
	RHOQ	ENST00000902923.1		c.201+6511G>C		intron	N/A	ENSP00000572982.1

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

African (AFR) AF: 0.282 AC: 11677 AN: 41452

American (AMR) AF: 0.321 AC: 4908 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3470

East Asian (EAS) AF: 0.0962 AC: 498 AN: 5178

South Asian (SAS) AF: 0.196 AC: 943 AN: 4816

European-Finnish (FIN) AF: 0.265 AC: 2799 AN: 10548

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21042 AN: 67974

Other (OTH) AF: 0.279 AC: 588 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.60
PhyloP100		-0.64
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: rs4952834; hg19: chr2-46777462;