17-61455992-C-G

Position:

• chr17-61455992-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321120.2(TBX4):​c.-3-496C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,124 control chromosomes in the GnomAD database, including 4,695 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4695 hom., cov: 33)
• Consequence: TBX4 NM_001321120.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX4	NM_001321120.2	c.-3-496C>G		intron_variant		ENST00000644296.1
LOC124904042	XR_007065872.1	n.2711G>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX4	ENST00000644296.1	c.-3-496C>G		intron_variant			NM_001321120.2	A1
TBX4	ENST00000589003.5	c.-125-632C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36159 AN: 152004 Hom.: 4695 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.238 AC: 36159 AN: 152124 Hom.: 4695 Cov.: 33 AF XY: 0.236 AC XY: 17548 AN XY: 74370

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.243

Alfa AF: 0.249 Hom.: 620

Bravo AF: 0.233

Asia WGS AF: 0.306 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11867179; hg19: chr17-59533353;