22-19783184-C-T

Variant names:

• chr22-19783184-C-T
• rs13055776
• ENST00000359500.7:c.*11-130C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.152
• Publications: 5 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]

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

Our verdict: Benign. The variant received -20 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 VariationId is 1222546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TBX1	NM_005992.1	c.*11-130C>T		intron_variant	Intron 9 of 9		NP_005983.1
GNB1L	NM_053004.3	c.*5525G>A		downstream_gene_variant		ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX1	ENST00000359500.7	c.*11-130C>T		intron_variant	Intron 9 of 9	1		ENSP00000352483.3
GNB1L	ENST00000329517.11	c.*5525G>A		downstream_gene_variant		1	NM_053004.3	ENSP00000331313.6

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

African (AFR) AF: 0.194 AC: 2841 AN: 14680

American (AMR) AF: 0.0456 AC: 1443 AN: 31648

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 1111 AN: 17370

East Asian (EAS) AF: 0.000609 AC: 19 AN: 31202

South Asian (SAS) AF: 0.0207 AC: 1162 AN: 56192

European-Finnish (FIN) AF: 0.0367 AC: 1172 AN: 31978

Middle Eastern (MID) AF: 0.0613 AC: 136 AN: 2220

European-Non Finnish (NFE) AF: 0.0654 AC: 19135 AN: 292708

Other (OTH) AF: 0.0682 AC: 1940 AN: 28446

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

African (AFR) AF: 0.191 AC: 7928 AN: 41522

American (AMR) AF: 0.0586 AC: 897 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 207 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5192

South Asian (SAS) AF: 0.0157 AC: 76 AN: 4828

European-Finnish (FIN) AF: 0.0356 AC: 378 AN: 10614

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0666 AC: 4528 AN: 68020

Other (OTH) AF: 0.0791 AC: 167 AN: 2110

Alfa AF: 0.0909 Hom.: 231

Bravo AF: 0.101

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.59
PhyloP100		-0.15
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: rs13055776; hg19: chr22-19770707;