rs5748417

Positions:

• chr22-19756987-T-C

Variant summary

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

The NM_080647.1(TBX1):​c.-87+242T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,758 control chromosomes in the GnomAD database, including 9,036 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 0.32 (9036 hom., cov: 31)
• Consequence: TBX1 NM_080647.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.78

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX1	NM_080647.1	c.-87+242T>C		intron_variant			NP_542378.1
TBX1	NM_080646.2	c.-87+242T>C		intron_variant			NP_542377.1
TBX1	NM_005992.1	c.-87+242T>C		intron_variant			NP_005983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX1	ENST00000332710.8	c.-87+242T>C		intron_variant		1		ENSP00000331791.4
TBX1	ENST00000329705.11	c.-87+242T>C		intron_variant		1		ENSP00000331176.7
TBX1	ENST00000359500.7	c.-87+242T>C		intron_variant		1		ENSP00000352483.3

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48276 AN: 151642 Hom.: 9027 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.318 AC: 48321 AN: 151758 Hom.: 9036 Cov.: 31 AF XY: 0.320 AC XY: 23725 AN XY: 74192

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.283

Alfa AF: 0.263 Hom.: 912

Bravo AF: 0.336

Asia WGS AF: 0.359 AC: 1243 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.016
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs5748417; hg19: chr22-19744510;