Variant 7-74743485-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_032999.4(GTF2I):c.1715G>A(p.Arg572Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 14)

Exomes 𝑓: 0.0028 ( 15 hom. )

Failed GnomAD Quality Control

Consequence

GTF2I
NM_032999.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.23

Variant links:

Genes affected

GTF2I (HGNC:4659): (general transcription factor IIi) This gene encodes a phosphoprotein containing six characteristic repeat motifs. The encoded protein binds to the initiator element (Inr) and E-box element in promoters and functions as a regulator of transcription. This locus, along with several other neighboring genes, is deleted in Williams-Beuren syndrome. There are many closely related genes and pseudogenes for this gene on chromosome 7. This gene also has pseudogenes on chromosomes 9, 13, and 21. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2013]

GTF2I links:

GTF2I (HGNC:):

GTF2I links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018974781).

BP6

Variant 7-74743485-G-A is Benign according to our data. Variant chr7-74743485-G-A is described in ClinVar as [Benign]. Clinvar id is 3388779.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2I	NM_032999.4 linkuse as main transcript	c.1715G>A	p.Arg572Gln	missense_variant	20/35	ENST00000573035.6	NP_127492.1	P78347-1X5DR09Q499G6A8K9W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2I	ENST00000573035.6 linkuse as main transcript	c.1715G>A	p.Arg572Gln	missense_variant	20/35	1	NM_032999.4	ENSP00000460070.1		P78347-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

248

AN:

104718

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000470

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000980

Gnomad ASJ

AF:

0.000415

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.000151

Gnomad MID

AF:

0.00510

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00164

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00283

AC:

1193

AN:

421908

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

642

AN XY:

232398

show subpopulations

Gnomad4 AFR exome

AF:

0.000749

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.0000419

Gnomad4 SAS exome

AF:

0.00199

Gnomad4 FIN exome

AF:

0.000847

Gnomad4 NFE exome

AF:

0.00400

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00237

AC:

248

AN:

104838

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

109

AN XY:

50504

show subpopulations

Gnomad4 AFR

AF:

0.000468

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000415

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00437

Gnomad4 FIN

AF:

0.000151

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00163

Alfa

AF:

0.00191

Hom.:

ExAC

AF:

0.000104

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

GTF2I: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

T;.;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.3

M;.;.;.

PrimateAI

Pathogenic

0.83

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

0.95

P;P;D;D

Vest4

0.69

MVP

0.92

ClinPred

0.10

GERP RS

5.0

Varity_R

0.29

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