Genetic Variant RHOXF2B:p.Gly82Ser (chrX-120077124-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001099685.3(RHOXF2B):c.244G>A(p.Gly82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 962,858 control chromosomes in the GnomAD database, including 22 homozygotes. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000082 ( 2 hom., 1 hem., cov: 14)

Exomes 𝑓: 0.00011 ( 22 hom. 25 hem. )

Failed GnomAD Quality Control

Consequence

RHOXF2B
NM_001099685.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.235

Publications

0 publications found

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:51582): (RHOXF1 antisense RNA 1)

RHOXF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049141943).

BP6

Variant X-120077124-C-T is Benign according to our data. Variant chrX-120077124-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661314.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 22 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099685.3. 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
	RHOXF2B	NM_001099685.3	MANE Select	c.244G>A	p.Gly82Ser	missense	Exon 2 of 4	NP_001093155.1	P0C7M4
	RHOXF1-AS1	NR_131238.1		n.297+40592C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOXF2B	ENST00000371402.5	TSL:1 MANE Select	c.244G>A	p.Gly82Ser	missense	Exon 2 of 4	ENSP00000360455.3	P0C7M4
	RHOXF1-AS1	ENST00000553843.5	TSL:2	n.297+40592C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000823

AC:

AN:

85099

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00230

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000457

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000316

AC:

AN:

151857

AF XY:

0.000144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00435

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000428

Gnomad OTH exome

AF:

0.000262

GnomAD4 exome

AF:

0.000107

AC:

103

AN:

962858

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

275030

show subpopulations

African (AFR)

AF:

0.0000436

AC:

AN:

22935

American (AMR)

AF:

0.0000704

AC:

AN:

28409

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16641

East Asian (EAS)

AF:

0.00336

AC:

AN:

21728

South Asian (SAS)

AF:

0.0000260

AC:

AN:

38494

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38267

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3693

European-Non Finnish (NFE)

AF:

0.0000253

AC:

AN:

752440

Other (OTH)

AF:

0.000174

AC:

AN:

40251

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000823

AC:

AN:

85099

Hom.:

Cov.:

AF XY:

0.0000502

AC XY:

AN XY:

19913

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22325

American (AMR)

AF:

0.00

AC:

AN:

7104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2064

East Asian (EAS)

AF:

0.00230

AC:

AN:

2177

South Asian (SAS)

AF:

0.00

AC:

AN:

1394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4475

Middle Eastern (MID)

AF:

0.00

AC:

AN:

179

European-Non Finnish (NFE)

AF:

0.0000457

AC:

AN:

43759

Other (OTH)

AF:

0.00

AC:

AN:

1071

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.000265

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.32

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.020

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.33

M_CAP

Benign

0.0082

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.34

PhyloP100

-0.23

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.76

REVEL

Benign

0.14

Sift

Benign

0.081

Sift4G

Benign

0.41

Polyphen

0.021

Vest4

0.090

MutPred

0.34

Gain of phosphorylation at G82 (P = 0.0123)

MVP

0.14

MPC

1.8

ClinPred

0.0083

Varity_R

0.097

gMVP

0.082

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over