Variant chr15-50301220-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 4P and 6B. PVS1_StrongBP6_ModerateBS2

The ENST00000220429.12(GABPB1):c.619+1G>T variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,612,706 control chromosomes in the GnomAD database, including 19 homozygotes. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0035 ( 19 hom. )

Consequence

GABPB1
ENST00000220429.12 splice_donor

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

GABPB1 (HGNC:4074): (GA binding protein transcription factor subunit beta 1) This gene encodes the GA-binding protein transcription factor, beta subunit. This protein forms a tetrameric complex with the alpha subunit, and stimulates transcription of target genes. The encoded protein may be involved in activation of cytochrome oxidase expression and nuclear control of mitochondrial function. The crystal structure of a similar protein in mouse has been resolved as a ternary protein complex. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GABPB1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.12373737 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.1, offset of -36, new splice context is: cagGTctgg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BP6

Variant 15-50301220-C-A is Benign according to our data. Variant chr15-50301220-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645327.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABPB1	NM_016654.5 linkuse as main transcript	c.583+37G>T		intron_variant		ENST00000380877.8	NP_057738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABPB1	ENST00000380877.8 linkuse as main transcript	c.583+37G>T		intron_variant		1	NM_016654.5	ENSP00000370259	P4	Q06547-2

Frequencies

GnomAD3 genomes

AF:

0.00296

AC:

450

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00356

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00390

AC:

977

AN:

250344

Hom.:

AF XY:

0.00443

AC XY:

599

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00707

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00423

Gnomad OTH exome

AF:

0.00475

GnomAD4 exome

AF:

0.00346

AC:

5052

AN:

1460434

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

2641

AN XY:

726402

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00301

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00696

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00326

Gnomad4 OTH exome

AF:

0.00380

GnomAD4 genome

AF:

0.00295

AC:

449

AN:

152272

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00356

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.00318

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00431

AC:

ExAC

AF:

0.00371

AC:

450

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00534

EpiControl

AF:

0.00599

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

GABPB1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.98

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

GERP RS

5.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over