rs13055776

chr22-19783184-C-T

Variant summary

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

The ENST00000359500.7(TBX1):c.*11-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 658,712 control chromosomes in the GnomAD database, including 2,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (993 hom., cov: 32)
  • Exomes 𝑓: 0.057 (1142 hom.)
• Consequence: TBX1 ENST00000359500.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.152

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]

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 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=-0.89).
• BP6: Variant 22-19783184-C-T is Benign according to our data. Variant chr22-19783184-C-T is described in ClinVar as [Benign]. Clinvar id is 1222546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX1	NM_005992.1	c.*11-130C>T		intron_variant
GNB1L	NM_053004.3			downstream_gene_variant		ENST00000329517.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX1	ENST00000359500.7	c.*11-130C>T		intron_variant		1		A2
GNB1L	ENST00000329517.11			downstream_gene_variant		1	NM_053004.3	P1

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 14292 AN: 152150 Hom.: 989 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0587

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0800

GnomAD4 exome AF: 0.0572 AC: 28959 AN: 506444 Hom.: 1142 Cov.: 0 AF XY: 0.0544 AC XY: 14742 AN XY: 270876

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.0456

Gnomad4 ASJ exome AF: 0.0640

Gnomad4 EAS exome AF: 0.000609

Gnomad4 SAS exome AF: 0.0207

Gnomad4 FIN exome AF: 0.0367

Gnomad4 NFE exome AF: 0.0654

Gnomad4 OTH exome AF: 0.0682

GnomAD4 genome AF: 0.0940 AC: 14315 AN: 152268 Hom.: 993 Cov.: 32 AF XY: 0.0902 AC XY: 6719 AN XY: 74458

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0586

Gnomad4 ASJ AF: 0.0596

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0886 Hom.: 204

Bravo AF: 0.101

Asia WGS AF: 0.0270 AC: 94 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	-0.89
Cadd	Benign	3.4
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13055776; hg19: chr22-19770707;