Genetic Variant GABPB2:p.Arg114His (chr1-151093256-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_144618.3(GABPB2):c.341G>A(p.Arg114His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000968 in 1,611,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

GABPB2
NM_144618.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.41

Variant links:

Genes affected

GABPB2 (HGNC:28441): (GA binding protein transcription factor subunit beta 2) Enables transcription cis-regulatory region binding activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GABPB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01221922).

BP6

Variant 1-151093256-G-A is Benign according to our data. Variant chr1-151093256-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2373676.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABPB2	NM_144618.3 link	c.341G>A	p.Arg114His	missense_variant	Exon 4 of 9	ENST00000368918.8	NP_653219.1	Q8TAK5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABPB2	ENST00000368918.8 link	c.341G>A	p.Arg114His	missense_variant	Exon 4 of 9	1	NM_144618.3	ENSP00000357914.3		Q8TAK5

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000966

AC:

AN:

248374

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

134284

show subpopulations

Gnomad AFR exome

AF:

0.000994

Gnomad AMR exome

AF:

0.0000598

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000610

AC:

AN:

1459260

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

725902

show subpopulations

Gnomad4 AFR exome

AF:

0.000870

Gnomad4 AMR exome

AF:

0.0000678

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000440

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000219

EpiControl

AF:

0.000179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 08, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.20

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.85

T;D

M_CAP

Benign

0.0093

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.98

N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.18

MVP

0.52

MPC

0.19

ClinPred

0.023

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.29

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