rs2301558

Positions:

chr22-19764306-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379200.1(TBX1):c.691C>T(p.Leu231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,612,690 control chromosomes in the GnomAD database, including 61,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 10424 hom., cov: 33)

Exomes 𝑓: 0.25 ( 50821 hom. )

Consequence

TBX1
NM_001379200.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: 0.0690

Variant links:

Genes affected

TBX1 (HGNC:11592): (T-box transcription factor 1) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene product shares 98% amino acid sequence identity with the mouse ortholog. DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), a common congenital disorder characterized by neural-crest-related developmental defects, has been associated with deletions of chromosome 22q11.2, where this gene has been mapped. Studies using mouse models of DiGeorge syndrome suggest a major role for this gene in the molecular etiology of DGS/VCFS. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

TBX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 22-19764306-C-T is Benign according to our data. Variant chr22-19764306-C-T is described in ClinVar as [Benign]. Clinvar id is 263383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19764306-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.069 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX1	NM_001379200.1 linkuse as main transcript	c.691C>T	p.Leu231=	synonymous_variant	3/7	ENST00000649276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX1	ENST00000649276.2 linkuse as main transcript	c.691C>T	p.Leu231=	synonymous_variant	3/7		NM_001379200.1	A2

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51241

AN:

152070

Hom.:

10388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.274

AC:

68669

AN:

250178

Hom.:

10795

AF XY:

0.274

AC XY:

37096

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.585

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.117

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.254

AC:

370397

AN:

1460502

Hom.:

50821

Cov.:

AF XY:

0.256

AC XY:

186342

AN XY:

726604

show subpopulations

Gnomad4 AFR exome

AF:

0.592

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.0987

Gnomad4 SAS exome

AF:

0.364

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.337

AC:

51334

AN:

152188

Hom.:

10424

Cov.:

AF XY:

0.335

AC XY:

24945

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.360

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.239

Gnomad4 OTH

AF:

0.326

Alfa

AF:

0.261

Hom.:

7726

Bravo

AF:

0.351

Asia WGS

AF:

0.270

AC:

939

AN:

3478

EpiCase

AF:

0.244

EpiControl

AF:

0.251

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

DiGeorge syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

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