17-61455905-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001321120.2(TBX4):c.-3-583T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 152,180 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0062 (4 hom., cov: 33)
• Consequence: TBX4 NM_001321120.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.969

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]

LOC124904042 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-61455905-T-C is Benign according to our data. Variant chr17-61455905-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2647998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00618 (940/152180) while in subpopulation NFE AF= 0.00956 (650/67984). AF 95% confidence interval is 0.00895. There are 4 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 940 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX4	NM_001321120.2	c.-3-583T>C		intron_variant		ENST00000644296.1
LOC124904042	XR_007065872.1	n.2798A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX4	ENST00000644296.1	c.-3-583T>C		intron_variant			NM_001321120.2	A1
TBX4	ENST00000589003.5	c.-125-719T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00618 AC: 940 AN: 152062 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00956

Gnomad OTH AF: 0.00432

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00618 AC: 940 AN: 152180 Hom.: 4 Cov.: 33 AF XY: 0.00571 AC XY: 425 AN XY: 74414

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.00956

Gnomad4 OTH AF: 0.00428

Alfa AF: 0.00672 Hom.: 1

Bravo AF: 0.00539

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

TBX4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	2.2
Dann	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75514233; hg19: chr17-59533266;