Variant 1-88857476-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001514.6(GTF2B):c.547G>A(p.Val183Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000319 in 1,567,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

GTF2B
NM_001514.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42

Variant links:

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]

GTF2B links:

GTF2B (HGNC:):

GTF2B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22257414).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2B	NM_001514.6 linkuse as main transcript	c.547G>A	p.Val183Ile	missense_variant	6/7	ENST00000370500.10	NP_001505.1	Q00403
GTF2B	XR_007059241.1 linkuse as main transcript	n.722G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GTF2B	ENST00000370500.10 linkuse as main transcript	c.547G>A	p.Val183Ile	missense_variant	6/7	1	NM_001514.6	ENSP00000359531.5	Q00403
GTF2B	ENST00000418217.1 linkuse as main transcript	c.532G>A	p.Val178Ile	missense_variant	6/6	5		ENSP00000402345.1	B1APE2
GTF2B	ENST00000448623.5 linkuse as main transcript	c.544G>A	p.Val182Ile	missense_variant	6/7	5		ENSP00000415741.1	B1APE1
GTF2B	ENST00000494819.5 linkuse as main transcript	n.682G>A		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000693

AC:

AN:

245248

Hom.:

AF XY:

0.0000676

AC XY:

AN XY:

133130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000992

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000311

AC:

AN:

1415092

Hom.:

Cov.:

AF XY:

0.0000354

AC XY:

AN XY:

706400

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.0000271

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000907

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.547G>A (p.V183I) alteration is located in exon 6 (coding exon 6) of the GTF2B gene. This alteration results from a G to A substitution at nucleotide position 547, causing the valine (V) at amino acid position 183 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;T;T

Eigen

Benign

-0.00086

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.030

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.077

B;.;.

Vest4

0.45

MutPred

0.65

Loss of catalytic residue at V183 (P = 0.0871);.;.;

MVP

0.66

MPC

0.82

ClinPred

0.074

GERP RS

4.6

Varity_R

0.33

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over