chr1-151090571-C-T

Variant names:

• chr1-151090571-C-T
• rs760608061
• NM_144618.3:c.274C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144618.3(GABPB2):​c.274C>T​(p.Arg92Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,208 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: 𝑓 0.000092 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: GABPB2 NM_144618.3 missense, splice_region
• Scores: Splicing: ADA: 0.9015
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20393911).

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.274C>T	p.Arg92Trp	missense splice_region	Exon 3 of 9	NP_653219.1	Q8TAK5
	GABPB2	NM_001323910.2		c.322C>T	p.Arg108Trp	missense splice_region	Exon 4 of 10	NP_001310839.1
	GABPB2	NM_001323906.2		c.274C>T	p.Arg92Trp	missense splice_region	Exon 3 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.274C>T	p.Arg92Trp	missense splice_region	Exon 3 of 9	ENSP00000357914.3	Q8TAK5
	GABPB2	ENST00000931884.1		c.322C>T	p.Arg108Trp	missense splice_region	Exon 4 of 10	ENSP00000601943.1
	GABPB2	ENST00000947109.1		c.322C>T	p.Arg108Trp	missense splice_region	Exon 4 of 10	ENSP00000617168.1

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152064 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000520 AC: 13 AN: 249878 AF XY: 0.0000814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000541 AC: 79 AN: 1461026 Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 49 AN XY: 726832

African (AFR) AF: 0.0000598 AC: 2 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39686

South Asian (SAS) AF: 0.000279 AC: 24 AN: 86142

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53390

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000387 AC: 43 AN: 1111552

Other (OTH) AF: 0.0000828 AC: 5 AN: 60364

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152182 Hom.: 0 Cov.: 30 AF XY: 0.0000806 AC XY: 6 AN XY: 74408

African (AFR) AF: 0.00 AC: 0 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000741 AC: 9

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.50		Gain of catalytic residue at L90 (P = 0.0053)
MVP		0.71
MPC		0.59
ClinPred		0.58	D
GERP RS		2.4
Varity_R		0.78
gMVP		0.50
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.90
dbscSNV1_RF	Benign	0.70
SpliceAI score (max)		0.18		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: rs760608061; hg19: chr1-151063047; COSMIC: COSV105287376; COSMIC: COSV105287376;