22-19759380-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000332710.8(TBX1):c.-86-178A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 627,472 control chromosomes in the GnomAD database, including 131,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (26790 hom., cov: 34)
  • Exomes 𝑓: 0.66 (104460 hom.)
• Consequence: TBX1 ENST00000332710.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.638

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 22-19759380-A-T is Benign according to our data. Variant chr22-19759380-A-T is described in ClinVar as [Benign]. Clinvar id is 1290981.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX1	NM_005992.1	c.-86-178A>T		intron_variant
TBX1	NM_080646.2	c.-86-178A>T		intron_variant
TBX1	NM_080647.1	c.-86-178A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX1	ENST00000329705.11	c.-86-178A>T		intron_variant		1		A2
TBX1	ENST00000332710.8	c.-86-178A>T		intron_variant		1		P2
TBX1	ENST00000359500.7	c.-86-178A>T		intron_variant		1		A2
TBX1	ENST00000680333.1	c.-86-178A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89296 AN: 151884 Hom.: 26767 Cov.: 34

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.660 AC: 313976 AN: 475474 Hom.: 104460 AF XY: 0.660 AC XY: 147421 AN XY: 223198

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.704

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.664

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.588 AC: 89369 AN: 151998 Hom.: 26790 Cov.: 34 AF XY: 0.586 AC XY: 43572 AN XY: 74294

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.594

Alfa AF: 0.615 Hom.: 3617

Bravo AF: 0.578

Asia WGS AF: 0.608 AC: 2115 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	11
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs737867; hg19: chr22-19746903;