Variant X-120077148-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001099685.3(RHOXF2B):c.220G>A(p.Gly74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000974 in 964,819 control chromosomes in the GnomAD database, including 14 homozygotes. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 1 hem., cov: 13)

Exomes 𝑓: 0.000097 ( 14 hom. 26 hem. )

Failed GnomAD Quality Control

Consequence

RHOXF2B
NM_001099685.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.849

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13832551).

BS2

High Homozygotes in GnomAdExome4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF2B	NM_001099685.3 linkuse as main transcript	c.220G>A	p.Gly74Ser	missense_variant	2/4	ENST00000371402.5	NP_001093155.1	P0C7M4
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.297+40616C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOXF2B	ENST00000371402.5 linkuse as main transcript	c.220G>A	p.Gly74Ser	missense_variant	2/4	1	NM_001099685.3	ENSP00000360455.3		P0C7M4
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.297+40616C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

79573

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

17291

FAILED QC

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000120

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000101

AC:

AN:

149218

Hom.:

AF XY:

0.0000835

AC XY:

AN XY:

47886

show subpopulations

Gnomad AFR exome

AF:

0.0000977

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000754

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000974

AC:

AN:

964819

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

275605

show subpopulations

Gnomad4 AFR exome

AF:

0.0000435

Gnomad4 AMR exome

AF:

0.0000352

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000520

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.0000248

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000113

AC:

AN:

79591

Hom.:

Cov.:

AF XY:

0.0000577

AC XY:

AN XY:

17323

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000121

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000510

Hom.:

ExAC

AF:

0.000101

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

Dec 21, 2023

The c.220G>A (p.G74S) 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 220, causing the glycine (G) at amino acid position 74 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.13

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0089

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.54

M_CAP

Benign

0.0099

MetaRNN

Benign

0.14

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.36

PROVEAN

Benign

0.57

REVEL

Benign

0.24

Sift

Uncertain

0.014

Sift4G

Uncertain

0.045

Polyphen

1.0

Vest4

0.13

MVP

0.12

MPC

2.8

ClinPred

0.055

GERP RS

0.88

Varity_R

0.090

gMVP

0.069

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