15-50328443-T-C

Variant names:

• chr15-50328443-T-C
• rs16963635
• NM_016654.5:c.1-18645A>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.1-18645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 152,260 control chromosomes in the GnomAD database, including 311 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 0.049 (311 hom., cov: 32)
• Consequence: GABPB1 NM_016654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 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.1-18645A>G		intron	N/A	NP_057738.1
	GABPB1	NM_001320910.2		c.-1+17929A>G		intron	N/A	NP_001307839.1
	GABPB1	NM_005254.6		c.1-18645A>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.1-18645A>G		intron	N/A	ENSP00000370259.3
	GABPB1	ENST00000220429.12	TSL:1	c.1-18645A>G		intron	N/A	ENSP00000220429.8
	GABPB1	ENST00000429662.6	TSL:1	c.1-18645A>G		intron	N/A	ENSP00000395771.2

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7430 AN: 152142 Hom.: 311 Cov.: 32

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0588

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0489 AC: 7441 AN: 152260 Hom.: 311 Cov.: 32 AF XY: 0.0523 AC XY: 3895 AN XY: 74436

African (AFR) AF: 0.0703 AC: 2921 AN: 41562

American (AMR) AF: 0.0590 AC: 901 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3466

East Asian (EAS) AF: 0.199 AC: 1029 AN: 5180

South Asian (SAS) AF: 0.0644 AC: 311 AN: 4828

European-Finnish (FIN) AF: 0.0814 AC: 863 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0186 AC: 1263 AN: 68014

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0245 Hom.: 30

Bravo AF: 0.0494

Asia WGS AF: 0.117 AC: 404 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.41
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16963635; hg19: chr15-50620640;