rs5748418

chr22-19757001-G-Achr22-19757001-G-C

Variant summary

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

The ENST00000332710.8(TBX1):c.-87+256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,924 control chromosomes in the GnomAD database, including 4,227 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 0.23 (4227 hom., cov: 32)
• Consequence: TBX1 ENST00000332710.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX1	NM_005992.1	c.-87+256G>A		intron_variant
TBX1	NM_080646.2	c.-87+256G>A		intron_variant
TBX1	NM_080647.1	c.-87+256G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX1	ENST00000329705.11	c.-87+256G>A		intron_variant		1		A2
TBX1	ENST00000332710.8	c.-87+256G>A		intron_variant		1		P2
TBX1	ENST00000359500.7	c.-87+256G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35282 AN: 151808 Hom.: 4227 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.232 AC: 35295 AN: 151924 Hom.: 4227 Cov.: 32 AF XY: 0.236 AC XY: 17527 AN XY: 74266

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.224

Alfa AF: 0.219 Hom.: 452

Bravo AF: 0.239

Asia WGS AF: 0.336 AC: 1163 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.9
Dann	Benign	0.85

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: rs5748418; hg19: chr22-19744524;