chr1-151097897-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144618.3(GABPB2):​c.517C>T​(p.Pro173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GABPB2
NM_144618.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.336
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06559783).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABPB2NM_144618.3 linkc.517C>T p.Pro173Ser missense_variant Exon 5 of 9 ENST00000368918.8 NP_653219.1 Q8TAK5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABPB2ENST00000368918.8 linkc.517C>T p.Pro173Ser missense_variant Exon 5 of 9 1 NM_144618.3 ENSP00000357914.3 Q8TAK5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461766
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.517C>T (p.P173S) alteration is located in exon 5 (coding exon 4) of the GABPB2 gene. This alteration results from a C to T substitution at nucleotide position 517, causing the proline (P) at amino acid position 173 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
0.083
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
6.5
DANN
Benign
0.59
DEOGEN2
Benign
0.039
T;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.28
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
M;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.57
N;N
REVEL
Benign
0.043
Sift
Benign
0.34
T;T
Sift4G
Benign
0.38
T;T
Polyphen
0.0010
B;B
Vest4
0.15
MutPred
0.39
Gain of loop (P = 0.0195);Gain of loop (P = 0.0195);
MVP
0.65
MPC
0.15
ClinPred
0.25
T
GERP RS
4.6
Varity_R
0.062
gMVP
0.59

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.

Other links and lift over

dbSNP: rs868080729; hg19: chr1-151070373; COSMIC: COSV105287382; API