chr22-19765450-C-T

Variant names:

• chr22-19765450-C-T
• rs2238773
• NM_001379200.1:c.868-308C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379200.1(TBX1):​c.868-308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,208 control chromosomes in the GnomAD database, including 3,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (3124 hom., cov: 33)
• Consequence: TBX1 NM_001379200.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.946
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-19765450-C-T is Benign according to our data. Variant chr22-19765450-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379200.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX1	NM_001379200.1	MANE Select	c.868-308C>T		intron	N/A	NP_001366129.1
	TBX1	NM_080647.1		c.841-308C>T		intron	N/A	NP_542378.1
	TBX1	NM_080646.2		c.841-308C>T		intron	N/A	NP_542377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX1	ENST00000649276.2	MANE Select	c.868-308C>T		intron	N/A	ENSP00000497003.1
	TBX1	ENST00000332710.8	TSL:1	c.841-308C>T		intron	N/A	ENSP00000331791.4
	TBX1	ENST00000329705.11	TSL:1	c.841-308C>T		intron	N/A	ENSP00000331176.7

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26426 AN: 152090 Hom.: 3126 Cov.: 33

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.174 AC: 26425 AN: 152208 Hom.: 3124 Cov.: 33 AF XY: 0.175 AC XY: 13052 AN XY: 74434

African (AFR) AF: 0.0428 AC: 1780 AN: 41584

American (AMR) AF: 0.264 AC: 4039 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2368 AN: 5138

South Asian (SAS) AF: 0.194 AC: 937 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1500 AN: 10606

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14063 AN: 67970

Other (OTH) AF: 0.193 AC: 409 AN: 2114

Alfa AF: 0.138 Hom.: 378

Bravo AF: 0.177

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2238773; hg19: chr22-19752973;