rs41298826

chr22-19764484-T-C

Variant summary

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

The NM_001379200.1(TBX1):c.711+158T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,206 control chromosomes in the GnomAD database, including 3,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3538 hom., cov: 33)
• Consequence: TBX1 NM_001379200.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.428

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=-0.92).
• BP6: Variant 22-19764484-T-C is Benign according to our data. Variant chr22-19764484-T-C is described in ClinVar as [Benign]. Clinvar id is 1257183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX1	NM_001379200.1	c.711+158T>C		intron_variant		ENST00000649276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX1	ENST00000649276.2	c.711+158T>C		intron_variant			NM_001379200.1	A2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28204 AN: 152088 Hom.: 3539 Cov.: 33

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.185 AC: 28203 AN: 152206 Hom.: 3538 Cov.: 33 AF XY: 0.188 AC XY: 13983 AN XY: 74404

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.204

Alfa AF: 0.211 Hom.: 608

Bravo AF: 0.187

Asia WGS AF: 0.312 AC: 1087 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

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	5.3
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs41298826; hg19: chr22-19752007; COSMIC: COSV60354841; COSMIC: COSV60354841;