1-88873739-C-T

Variant names:

• chr1-88873739-C-T
• rs7538427
• NM_001514.6:c.125-9625G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001514.6(GTF2B):​c.125-9625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.931 in 152,108 control chromosomes in the GnomAD database, including 66,072 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 0.93 (66072 hom., cov: 30)
• Consequence: GTF2B NM_001514.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 3 publications found

Genes affected

GTF2B (HGNC:4648): (general transcription factor IIB) This gene encodes the general transcription factor IIB, one of the ubiquitous factors required for transcription initiation by RNA polymerase II. The protein localizes to the nucleus where it forms a complex (the DAB complex) with transcription factors IID and IIA. Transcription factor IIB serves as a bridge between IID, the factor which initially recognizes the promoter sequence, and RNA polymerase II. [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 (SAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2B	NM_001514.6	c.125-9625G>A		intron_variant	Intron 2 of 6	ENST00000370500.10	NP_001505.1
GTF2B	XR_007059241.1	n.193-9625G>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2B	ENST00000370500.10	c.125-9625G>A		intron_variant	Intron 2 of 6	1	NM_001514.6	ENSP00000359531.5

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141539 AN: 151990 Hom.: 66019 Cov.: 30

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.931 AC: 141649 AN: 152108 Hom.: 66072 Cov.: 30 AF XY: 0.933 AC XY: 69326 AN XY: 74324

African (AFR) AF: 0.885 AC: 36713 AN: 41492

American (AMR) AF: 0.956 AC: 14602 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3305 AN: 3472

East Asian (EAS) AF: 0.873 AC: 4515 AN: 5172

South Asian (SAS) AF: 0.956 AC: 4600 AN: 4810

European-Finnish (FIN) AF: 0.961 AC: 10160 AN: 10572

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64624 AN: 68002

Other (OTH) AF: 0.935 AC: 1972 AN: 2110

Alfa AF: 0.937 Hom.: 10623

Bravo AF: 0.928

Asia WGS AF: 0.874 AC: 3039 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	0.95
DANN	Benign	0.39
PhyloP100		-0.39
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: rs7538427; hg19: chr1-89339422;