Variant chr7-74752088-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PVS1_ModeratePP3_StrongBP6_Moderate

The NM_032999.4(GTF2I):c.2477-2A>G variant causes a splice acceptor change. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 17)

Exomes 𝑓: 0.0013 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

GTF2I
NM_032999.4 splice_acceptor

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.36

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.02669336 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 7-74752088-A-G is Benign according to our data. Variant chr7-74752088-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657598.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2I	NM_032999.4 linkuse as main transcript	c.2477-2A>G		splice_acceptor_variant		ENST00000573035.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2I	ENST00000573035.6 linkuse as main transcript	c.2477-2A>G		splice_acceptor_variant		1	NM_032999.4		P78347-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

108

AN:

107820

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000440

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00168

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.00126

AC:

AN:

51438

Hom.:

AF XY:

0.00107

AC XY:

AN XY:

25190

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000717

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000224

Gnomad FIN exome

AF:

0.00296

Gnomad NFE exome

AF:

0.00180

Gnomad OTH exome

AF:

0.000603

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00128

AC:

706

AN:

553414

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

362

AN XY:

298410

show subpopulations

Gnomad4 AFR exome

AF:

0.0000971

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000241

Gnomad4 FIN exome

AF:

0.00153

Gnomad4 NFE exome

AF:

0.00173

Gnomad4 OTH exome

AF:

0.000840

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00100

AC:

108

AN:

107920

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

AN XY:

50776

show subpopulations

Gnomad4 AFR

AF:

0.000133

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000441

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00168

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000865

Hom.:

ExAC

AF:

0.000793

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

GTF2I: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Benign

0.96

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

D;D;D;D

GERP RS

5.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.77

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.99

Position offset: 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