15-50296560-T-C

Variant names:

• chr15-50296560-T-C
• rs6493427
• NM_016654.5:c.697+4229A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016654.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABPB1	NM_016654.5	MANE Select	c.697+4229A>G		intron	N/A	NP_057738.1
	GABPB1	NM_001320910.2		c.733+4229A>G		intron	N/A	NP_001307839.1
	GABPB1	NM_005254.6		c.733+4229A>G		intron	N/A	NP_005245.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABPB1	ENST00000380877.8	TSL:1 MANE Select	c.697+4229A>G		intron	N/A	ENSP00000370259.3
	GABPB1	ENST00000220429.12	TSL:1	c.733+4229A>G		intron	N/A	ENSP00000220429.8
	GABPB1	ENST00000429662.6	TSL:1	c.733+4229A>G		intron	N/A	ENSP00000395771.2

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

African (AFR) AF: 0.832 AC: 34522 AN: 41504

American (AMR) AF: 0.666 AC: 10171 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2454 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1816 AN: 5178

South Asian (SAS) AF: 0.546 AC: 2634 AN: 4826

European-Finnish (FIN) AF: 0.465 AC: 4904 AN: 10538

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40498 AN: 67922

Other (OTH) AF: 0.643 AC: 1356 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6493427; hg19: chr15-50588757;