17-61457626-T-G

Position:

chr17-61457626-T-G

Variant summary

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

The NM_001321120.2(TBX4):c.276T>G(p.Ala92Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,612,722 control chromosomes in the GnomAD database, including 26,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2379 hom., cov: 32)

Exomes 𝑓: 0.17 ( 23737 hom. )

Consequence

TBX4
NM_001321120.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.106

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:

LOC124904042 (HGNC:):

LOC124904042 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=-0.48).

BP6

Variant 17-61457626-T-G is Benign according to our data. Variant chr17-61457626-T-G is described in ClinVar as [Benign]. Clinvar id is 324249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61457626-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.106 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX4	NM_001321120.2 link	c.276T>G	p.Ala92Ala	synonymous_variant	3/9	ENST00000644296.1	NP_001308049.1	P57082-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBX4	ENST00000644296.1 link	c.276T>G	p.Ala92Ala	synonymous_variant	3/9		NM_001321120.2	ENSP00000495986.1	P57082-2
TBX4	ENST00000240335.1 link	c.276T>G	p.Ala92Ala	synonymous_variant	2/8	1		ENSP00000240335.1	P57082-1
TBX4	ENST00000642491.1 link	c.276T>G	p.Ala92Ala	synonymous_variant	2/8			ENSP00000495714.1	P57082-2
TBX4	ENST00000589003.5 link	c.18T>G	p.Ala6Ala	synonymous_variant	3/6	3		ENSP00000467588.1	K7EPY2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25245

AN:

151516

Hom.:

2372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.192

AC:

48109

AN:

251124

Hom.:

5073

AF XY:

0.191

AC XY:

25935

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.332

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.174

AC:

253722

AN:

1461088

Hom.:

23737

Cov.:

AF XY:

0.175

AC XY:

126997

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.378

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.277

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.167

AC:

25275

AN:

151634

Hom.:

2379

Cov.:

AF XY:

0.173

AC XY:

12840

AN XY:

74090

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.159

Hom.:

1273

Bravo

AF:

0.157

Asia WGS

AF:

0.258

AC:

898

AN:

3478

EpiCase

AF:

0.154

EpiControl

AF:

0.154

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

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 -

Coxopodopatellar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

-0.48

CADD

Benign

DANN

Benign

0.69

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