Variant X-120077118-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001099685.3(RHOXF2B):c.250G>A(p.Gly84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000609 in 1,050,523 control chromosomes in the GnomAD database, including 8 homozygotes. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., 0 hem., cov: 14)

Exomes 𝑓: 0.000052 ( 7 hom. 14 hem. )

Consequence

RHOXF2B
NM_001099685.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.184

Variant links:

Genes affected

RHOXF2B (HGNC:33519): (Rhox homeobox family member 2B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in positive regulation of gene expression. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

RHOXF2B links:

RHOXF1-AS1 (HGNC:):

RHOXF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053393513).

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF2B	NM_001099685.3 linkuse as main transcript	c.250G>A	p.Gly84Arg	missense_variant	2/4	ENST00000371402.5	NP_001093155.1	P0C7M4
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.297+40586C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOXF2B	ENST00000371402.5 linkuse as main transcript	c.250G>A	p.Gly84Arg	missense_variant	2/4	1	NM_001099685.3	ENSP00000360455.3		P0C7M4
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.297+40586C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000163

AC:

AN:

86146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20342

show subpopulations

Gnomad AFR

AF:

0.000310

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000277

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000904

Gnomad OTH

AF:

0.000911

GnomAD3 exomes

AF:

0.000118

AC:

AN:

152274

Hom.:

AF XY:

0.0000616

AC XY:

AN XY:

48676

show subpopulations

Gnomad AFR exome

AF:

0.000808

Gnomad AMR exome

AF:

0.000227

Gnomad ASJ exome

AF:

0.000470

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000518

AC:

AN:

964377

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

275285

show subpopulations

Gnomad4 AFR exome

AF:

0.000392

Gnomad4 AMR exome

AF:

0.000176

Gnomad4 ASJ exome

AF:

0.000300

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000520

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000305

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000163

AC:

AN:

86146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20342

show subpopulations

Gnomad4 AFR

AF:

0.000310

Gnomad4 AMR

AF:

0.000277

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000904

Gnomad4 OTH

AF:

0.000911

Alfa

AF:

0.0000458

Hom.:

ESP6500AA

AF:

0.000569

AC:

ESP6500EA

AF:

0.000324

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 28, 2022

The c.250G>A (p.G84R) alteration is located in exon 2 (coding exon 2) of the RHOXF2B gene. This alteration results from a G to A substitution at nucleotide position 250, causing the glycine (G) at amino acid position 84 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.32

M_CAP

Benign

0.011

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.97

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.27

REVEL

Benign

0.28

Sift

Uncertain

0.020

Sift4G

Uncertain

0.018

Polyphen

0.97

Vest4

0.097

MutPred

0.38

Gain of solvent accessibility (P = 0.0055);

MVP

0.043

MPC

2.7

ClinPred

0.024

GERP RS

-0.20

Varity_R

0.11

gMVP

0.083

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over