1-151093328-A-G

Variant names:

• chr1-151093328-A-G
• NM_144618.3:c.413A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144618.3(GABPB2):​c.413A>G​(p.Lys138Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GABPB2 NM_144618.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.25
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABPB2	NM_144618.3	MANE Select	c.413A>G	p.Lys138Arg	missense	Exon 4 of 9	NP_653219.1	Q8TAK5
	GABPB2	NM_001323910.2		c.461A>G	p.Lys154Arg	missense	Exon 5 of 10	NP_001310839.1
	GABPB2	NM_001323906.2		c.413A>G	p.Lys138Arg	missense	Exon 4 of 10	NP_001310835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABPB2	ENST00000368918.8	TSL:1 MANE Select	c.413A>G	p.Lys138Arg	missense	Exon 4 of 9	ENSP00000357914.3	Q8TAK5
	GABPB2	ENST00000467551.1	TSL:1	n.83A>G		non_coding_transcript_exon	Exon 1 of 4
	GABPB2	ENST00000931884.1		c.461A>G	p.Lys154Arg	missense	Exon 5 of 10	ENSP00000601943.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
PhyloP100		9.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.23
Sift	Benign	0.034	D
Sift4G	Benign	0.072	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.41		Loss of ubiquitination at K138 (P = 0.0283)
MVP		0.42
MPC		0.57
ClinPred		0.97	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.48
Mutation Taster		=43/57	disease causing

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

Other links and lift over

hg19: chr1-151065804;