rs2238776

Variant names:

• chr22-19770369-G-A
• rs2238776
• ENST00000329705.11:c.1009+4367G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-19770369-G-A
• chr22-19770369-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000329705.11(TBX1):​c.1009+4367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,232 control chromosomes in the GnomAD database, including 3,065 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 0.17 (3065 hom., cov: 33)
• Consequence: TBX1 ENST00000329705.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 32 publications found

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]

TBX1 Gene-Disease associations (from GenCC):

• conotruncal heart malformations

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• DiGeorge syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• velocardiofacial syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX1	NM_080646.2	c.1009+4367G>A		intron_variant	Intron 8 of 8		NP_542377.1
TBX1	NM_005992.1	c.1009+4367G>A		intron_variant	Intron 8 of 9		NP_005983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX1	ENST00000329705.11	c.1009+4367G>A		intron_variant	Intron 8 of 8	1		ENSP00000331176.7
TBX1	ENST00000359500.7	c.1009+4367G>A		intron_variant	Intron 8 of 9	1		ENSP00000352483.3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26227 AN: 152114 Hom.: 3068 Cov.: 33

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.172 AC: 26225 AN: 152232 Hom.: 3065 Cov.: 33 AF XY: 0.174 AC XY: 12933 AN XY: 74426

African (AFR) AF: 0.0428 AC: 1780 AN: 41562

American (AMR) AF: 0.264 AC: 4033 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3468

East Asian (EAS) AF: 0.454 AC: 2349 AN: 5176

South Asian (SAS) AF: 0.191 AC: 923 AN: 4822

European-Finnish (FIN) AF: 0.138 AC: 1462 AN: 10610

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13942 AN: 67986

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.179 Hom.: 1016

Bravo AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.44
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2238776; hg19: chr22-19757892;