chr15-50296361-A-G

Position:

• chr15-50296361-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016654.5(GABPB1):​c.697+4428T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,200 control chromosomes in the GnomAD database, including 6,489 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 (6489 hom., cov: 33)
• Consequence: GABPB1 NM_016654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• 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.697+4428T>C		intron_variant		ENST00000380877.8	NP_057738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABPB1	ENST00000380877.8	c.697+4428T>C		intron_variant		1	NM_016654.5	ENSP00000370259	P4

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39424 AN: 152082 Hom.: 6492 Cov.: 33

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.00654

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.389

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: 0.259 AC: 39418 AN: 152200 Hom.: 6489 Cov.: 33 AF XY: 0.254 AC XY: 18940 AN XY: 74426

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.00655

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.280

Alfa AF: 0.342 Hom.: 12040

Bravo AF: 0.262

Asia WGS AF: 0.115 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.8
DANN	Benign	0.90

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: rs6493426; hg19: chr15-50588558;