Genetic Variant NM_144618.3:c.473A>G (chr1-151097853-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_144618.3(GABPB2):c.473A>G(p.Glu158Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GABPB2
NM_144618.3 missense, splice_region

Scores

Splicing: ADA: 0.8385

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3751974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144618.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GABPB2	NM_144618.3	MANE Select	c.473A>G	p.Glu158Gly	missense splice_region	Exon 5 of 9	NP_653219.1	Q8TAK5
GABPB2	NM_001323910.2		c.521A>G	p.Glu174Gly	missense splice_region	Exon 6 of 10	NP_001310839.1
GABPB2	NM_001323906.2		c.473A>G	p.Glu158Gly	missense splice_region	Exon 5 of 10	NP_001310835.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GABPB2	ENST00000368918.8	TSL:1 MANE Select	c.473A>G	p.Glu158Gly	missense splice_region	Exon 5 of 9	ENSP00000357914.3	Q8TAK5
GABPB2	ENST00000467551.1	TSL:1	n.143A>G		splice_region non_coding_transcript_exon	Exon 2 of 4
GABPB2	ENST00000931884.1		c.521A>G	p.Glu174Gly	missense splice_region	Exon 6 of 10	ENSP00000601943.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461426

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111720

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.71

M_CAP

Benign

0.021

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.4

PhyloP100

2.2

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.24

Sift

Benign

0.16

Sift4G

Benign

0.13

Polyphen

0.92

Vest4

0.51

MutPred

0.43

Gain of catalytic residue at M160 (P = 0.027)

MVP

0.91

MPC

0.24

ClinPred

0.97

GERP RS

5.2

Varity_R

0.21

gMVP

0.58

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.84

dbscSNV1_RF

Benign

0.46

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over