rs2238775

Variant names:

• chr22-19769849-G-A
• rs2238775
• ENST00000329705.11:c.1009+3847G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-19769849-G-A
• chr22-19769849-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080646.2(TBX1):​c.1009+3847G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,196 control chromosomes in the GnomAD database, including 21,365 homozygotes. 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: 𝑓 0.52 (21365 hom., cov: 34)
• Consequence: TBX1 NM_080646.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 1 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, STRONG Submitted by: PanelApp Australia, 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080646.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX1	NM_080646.2		c.1009+3847G>A		intron	N/A	NP_542377.1	O43435-1
	TBX1	NM_005992.1		c.1009+3847G>A		intron	N/A	NP_005983.1	O43435-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX1	ENST00000329705.11	TSL:1	c.1009+3847G>A		intron	N/A	ENSP00000331176.7	O43435-1
	TBX1	ENST00000359500.7	TSL:1	c.1009+3847G>A		intron	N/A	ENSP00000352483.3	O43435-2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79514 AN: 152076 Hom.: 21331 Cov.: 34

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.523 AC: 79606 AN: 152196 Hom.: 21365 Cov.: 34 AF XY: 0.522 AC XY: 38857 AN XY: 74426

African (AFR) AF: 0.624 AC: 25898 AN: 41512

American (AMR) AF: 0.582 AC: 8903 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2961 AN: 5174

South Asian (SAS) AF: 0.554 AC: 2674 AN: 4824

European-Finnish (FIN) AF: 0.378 AC: 3999 AN: 10592

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31439 AN: 68002

Other (OTH) AF: 0.536 AC: 1135 AN: 2116

Alfa AF: 0.493 Hom.: 2375

Bravo AF: 0.541

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.77
PhyloP100		-0.43
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: rs2238775; hg19: chr22-19757372;