22-19759962-G-C

Variant summary

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

The ENST00000332710.8(TBX1):c.34+285G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 152,280 control chromosomes in the GnomAD database, including 828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.058 (828 hom., cov: 33)
• Consequence: TBX1 ENST00000332710.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.129

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=-0.83).
• BP6: Variant 22-19759962-G-C is Benign according to our data. Variant chr22-19759962-G-C is described in ClinVar as [Benign]. Clinvar id is 1234968.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX1	NM_005992.1	c.34+285G>C		intron_variant
TBX1	NM_080646.2	c.34+285G>C		intron_variant
TBX1	NM_080647.1	c.34+285G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX1	ENST00000329705.11	c.34+285G>C		intron_variant		1		A2
TBX1	ENST00000332710.8	c.34+285G>C		intron_variant		1		P2
TBX1	ENST00000359500.7	c.34+285G>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8708 AN: 152162 Hom.: 813 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.0387

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

GnomAD4 genome AF: 0.0575 AC: 8759 AN: 152280 Hom.: 828 Cov.: 33 AF XY: 0.0562 AC XY: 4182 AN XY: 74468

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000970

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.00157 Hom.: 3

Bravo AF: 0.0646

Asia WGS AF: 0.0140 AC: 50 AN: 3478

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 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.52

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: rs12158927; hg19: chr22-19747485;