15-50347251-A-G

Variant names:

• chr15-50347251-A-G
• rs11637901
• NM_016654.5:c.-1+7734T>C

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+7734T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,862 control chromosomes in the GnomAD database, including 19,588 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 0.49 (19588 hom., cov: 30)
• Consequence: GABPB1 NM_016654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912
• Publications: 5 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]

RNU6-94P (HGNC:47057): (RNA, U6 small nuclear 94, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 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+7734T>C		intron	N/A	NP_057738.1
	GABPB1	NM_001320910.2		c.-24-856T>C		intron	N/A	NP_001307839.1
	GABPB1	NM_005254.6		c.-1+7734T>C		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+7734T>C		intron	N/A	ENSP00000370259.3
	GABPB1	ENST00000220429.12	TSL:1	c.-1+7734T>C		intron	N/A	ENSP00000220429.8
	GABPB1	ENST00000429662.6	TSL:1	c.-1+7734T>C		intron	N/A	ENSP00000395771.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74900 AN: 151744 Hom.: 19568 Cov.: 30

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.494 AC: 74969 AN: 151862 Hom.: 19588 Cov.: 30 AF XY: 0.483 AC XY: 35869 AN XY: 74228

African (AFR) AF: 0.421 AC: 17410 AN: 41380

American (AMR) AF: 0.557 AC: 8495 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2356 AN: 3466

East Asian (EAS) AF: 0.0559 AC: 289 AN: 5170

South Asian (SAS) AF: 0.459 AC: 2211 AN: 4818

European-Finnish (FIN) AF: 0.371 AC: 3902 AN: 10510

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38428 AN: 67964

Other (OTH) AF: 0.520 AC: 1099 AN: 2112

Alfa AF: 0.514 Hom.: 2713

Bravo AF: 0.507

Asia WGS AF: 0.258 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.42
PhyloP100		-0.91
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: rs11637901; hg19: chr15-50639448;