rs12909202

Positions:

• chr15-50320537-C-A
• chr15-50320537-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016654.5(GABPB1):​c.1-10739G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,136 control chromosomes in the GnomAD database, including 6,481 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6481 hom., cov: 32)
• Consequence: GABPB1 NM_016654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABPB1	NM_016654.5	c.1-10739G>T		intron_variant		ENST00000380877.8	NP_057738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABPB1	ENST00000380877.8	c.1-10739G>T		intron_variant		1	NM_016654.5	ENSP00000370259	P4

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39226 AN: 152018 Hom.: 6484 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.00654

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.258 AC: 39216 AN: 152136 Hom.: 6481 Cov.: 32 AF XY: 0.254 AC XY: 18853 AN XY: 74368

Gnomad4 AFR AF: 0.0781

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.00656

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.280

Alfa AF: 0.268 Hom.: 1484

Bravo AF: 0.261

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.1
DANN	Benign	0.92

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

Other links and lift over

dbSNP: rs12909202; hg19: chr15-50612734;