rs12923

Positions:

• chr15-50277839-A-G

Variant summary

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

The NM_016654.5(GABPB1):​c.*793T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,584 control chromosomes in the GnomAD database, including 2,210 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 0.16 (2208 hom., cov: 32)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: GABPB1 NM_016654.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478

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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABPB1	NM_016654.5	c.*793T>C		3_prime_UTR_variant	9/9	ENST00000380877.8	NP_057738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABPB1	ENST00000380877.8	c.*793T>C		3_prime_UTR_variant	9/9	1	NM_016654.5	ENSP00000370259	P4
GABPB1	ENST00000220429.12	c.*793T>C		3_prime_UTR_variant	9/9	1		ENSP00000220429	A1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24881 AN: 152048 Hom.: 2206 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.110 AC: 46 AN: 420 Hom.: 2 Cov.: 0 AF XY: 0.113 AC XY: 29 AN XY: 256

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.164 AC: 24913 AN: 152164 Hom.: 2208 Cov.: 32 AF XY: 0.161 AC XY: 11986 AN XY: 74408

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.0490

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.178

Alfa AF: 0.162 Hom.: 1178

Bravo AF: 0.170

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.78

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: rs12923; hg19: chr15-50570036;