rs1025906958

Variant names:

• chr1-151093336-T-A
• rs1025906958
• NM_144618.3:c.421T>A

Variant summary

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

The NM_144618.3(GABPB2):​c.421T>A​(p.Phe141Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,611,132 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GABPB2 NM_144618.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08
• 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.421T>A	p.Phe141Ile	missense	Exon 4 of 9	NP_653219.1	Q8TAK5
	GABPB2	NM_001323910.2		c.469T>A	p.Phe157Ile	missense	Exon 5 of 10	NP_001310839.1
	GABPB2	NM_001323906.2		c.421T>A	p.Phe141Ile	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.421T>A	p.Phe141Ile	missense	Exon 4 of 9	ENSP00000357914.3	Q8TAK5
	GABPB2	ENST00000467551.1	TSL:1	n.91T>A		non_coding_transcript_exon	Exon 1 of 4
	GABPB2	ENST00000931884.1		c.469T>A	p.Phe157Ile	missense	Exon 5 of 10	ENSP00000601943.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458952 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725724

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 85512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110980

Other (OTH) AF: 0.0000166 AC: 1 AN: 60278

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Uncertain	0.48
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.063	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.1
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.19
Sift	Benign	0.33	T
Sift4G	Benign	0.52	T
Polyphen		0.28	B
Vest4		0.68
MutPred		0.63		Gain of catalytic residue at F141 (P = 0.0515)
MVP		0.53
MPC		0.21
ClinPred		0.76	D
GERP RS		5.2
Varity_R		0.22
gMVP		0.75
Mutation Taster		=66/34	polymorphism

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

dbSNP: rs1025906958; hg19: chr1-151065812;