rs2270150

Positions:

chr17-61483324-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001321120.2(TBX4):c.1449C>T(p.Val483=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,610,470 control chromosomes in the GnomAD database, including 14,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1368 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12709 hom. )

Consequence

TBX4
NM_001321120.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.00300

Variant links:

Genes affected

TBX4 (HGNC:11603): (T-box transcription factor 4) 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 is the human homolog of mouse Tbx4, which is closely linked to Tbx2 on mouse chromosome 11. Similarly this gene, like TBX2, maps to human chromosome 17. Expression studies in mouse and chicken show that Tbx4 is expressed in developing hindlimb, but not in forelimb buds, suggesting a role for this gene in regulating limb development and specification of limb identity. [provided by RefSeq, Jul 2008]

TBX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 17-61483324-C-T is Benign according to our data. Variant chr17-61483324-C-T is described in ClinVar as [Benign]. Clinvar id is 261033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61483324-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.003 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBX4	NM_001321120.2 linkuse as main transcript	c.1449C>T	p.Val483=	synonymous_variant	9/9	ENST00000644296.1	NP_001308049.1
TBX4	NM_018488.3 linkuse as main transcript	c.1446C>T	p.Val482=	synonymous_variant	8/8		NP_060958.2
TBX4	XM_011525490.3 linkuse as main transcript	c.1638C>T	p.Val546=	synonymous_variant	9/9		XP_011523792.1
TBX4	XM_011525491.3 linkuse as main transcript	c.1635C>T	p.Val545=	synonymous_variant	9/9		XP_011523793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX4	ENST00000644296.1 linkuse as main transcript	c.1449C>T	p.Val483=	synonymous_variant	9/9		NM_001321120.2	ENSP00000495986	A1	P57082-2
TBX4	ENST00000240335.1 linkuse as main transcript	c.1446C>T	p.Val482=	synonymous_variant	8/8	1		ENSP00000240335	P4	P57082-1
TBX4	ENST00000589449.5 linkuse as main transcript	n.1115C>T		non_coding_transcript_exon_variant	8/8	1
TBX4	ENST00000642491.1 linkuse as main transcript	c.1449C>T	p.Val483=	synonymous_variant	8/8			ENSP00000495714	A1	P57082-2

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19428

AN:

152094

Hom.:

1365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.0922

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.113

AC:

28301

AN:

250294

Hom.:

1774

AF XY:

0.115

AC XY:

15527

AN XY:

135250

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.0648

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.0196

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.130

AC:

189627

AN:

1458258

Hom.:

12709

Cov.:

AF XY:

0.130

AC XY:

94008

AN XY:

724694

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0682

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.0321

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.128

AC:

19437

AN:

152212

Hom.:

1368

Cov.:

AF XY:

0.126

AC XY:

9378

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.0921

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.0193

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.135

Hom.:

2414

Bravo

AF:

0.123

Asia WGS

AF:

0.0830

AC:

290

AN:

3478

EpiCase

AF:

0.139

EpiControl

AF:

0.141

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 04, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

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: MAF -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Coxopodopatellar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.2

DANN

Benign

0.74

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