rs2238777

chr22-19770705-A-Gchr22-19770705-A-T

Variant summary

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

The ENST00000329705.11(TBX1):c.1009+4703A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,068 control chromosomes in the GnomAD database, including 22,348 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 0.54 (22348 hom., cov: 32)
• Consequence: TBX1 ENST00000329705.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX1	NM_005992.1	c.1009+4703A>G		intron_variant
TBX1	NM_080646.2	c.1009+4703A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX1	ENST00000329705.11	c.1009+4703A>G		intron_variant		1		A2
TBX1	ENST00000359500.7	c.1009+4703A>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81378 AN: 151950 Hom.: 22314 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.536 AC: 81470 AN: 152068 Hom.: 22348 Cov.: 32 AF XY: 0.536 AC XY: 39814 AN XY: 74318

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.548

Alfa AF: 0.496 Hom.: 20048

Bravo AF: 0.551

Asia WGS AF: 0.586 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	9.1
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2238777; hg19: chr22-19758228;