15-50296560-T-C

Position:

• chr15-50296560-T-C

Variant summary

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

The NM_016654.5(GABPB1):​c.697+4229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,018 control chromosomes in the GnomAD database, including 33,675 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 0.65 (33675 hom., cov: 31)
• Consequence: GABPB1 NM_016654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABPB1	NM_016654.5	c.697+4229A>G		intron_variant		ENST00000380877.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABPB1	ENST00000380877.8	c.697+4229A>G		intron_variant		1	NM_016654.5	P4

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99062 AN: 151900 Hom.: 33633 Cov.: 31

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.652 AC: 99157 AN: 152018 Hom.: 33675 Cov.: 31 AF XY: 0.641 AC XY: 47647 AN XY: 74302

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.643

Alfa AF: 0.389 Hom.: 641

Bravo AF: 0.680

Asia WGS AF: 0.460 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6493427; hg19: chr15-50588757;