rs72646948

Variant names:

• chr22-19759510-C-A
• rs72646948
• ENST00000332710.8:c.-86-48C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-19759510-C-A
• chr22-19759510-C-G
• chr22-19759510-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000332710.8(TBX1):​c.-86-48C>A variant causes a intron change. The variant allele was found at a frequency of 0.000000734 in 1,362,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TBX1 ENST00000332710.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX1	NM_080647.1	c.-86-48C>A		intron_variant	Intron 1 of 8		NP_542378.1
TBX1	NM_080646.2	c.-86-48C>A		intron_variant	Intron 1 of 8		NP_542377.1
TBX1	NM_005992.1	c.-86-48C>A		intron_variant	Intron 1 of 9		NP_005983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX1	ENST00000332710.8	c.-86-48C>A		intron_variant	Intron 1 of 8	1		ENSP00000331791.4
TBX1	ENST00000329705.11	c.-86-48C>A		intron_variant	Intron 1 of 8	1		ENSP00000331176.7
TBX1	ENST00000359500.7	c.-86-48C>A		intron_variant	Intron 1 of 9	1		ENSP00000352483.3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1362212 Hom.: 0 Cov.: 29 AF XY: 0.00000149 AC XY: 1 AN XY: 670462

African (AFR) AF: 0.00 AC: 0 AN: 29882

American (AMR) AF: 0.00 AC: 0 AN: 33814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23850

East Asian (EAS) AF: 0.00 AC: 0 AN: 34586

South Asian (SAS) AF: 0.00 AC: 0 AN: 76994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4162

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067476

Other (OTH) AF: 0.00 AC: 0 AN: 56668

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.97
PhyloP100		4.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs72646948; hg19: chr22-19747033;