Variant 21-44297667-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000291582.6(AIRE):c.1578T>C(p.Asp526=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,611,030 control chromosomes in the GnomAD database, including 155,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19394 hom., cov: 33)

Exomes 𝑓: 0.43 ( 135917 hom. )

Consequence

AIRE
ENST00000291582.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.97

Variant links:

Genes affected

AIRE (HGNC:360): (autoimmune regulator) This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]

AIRE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 21-44297667-T-C is Benign according to our data. Variant chr21-44297667-T-C is described in ClinVar as [Benign]. Clinvar id is 128337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44297667-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIRE	NM_000383.4 linkuse as main transcript	c.1578T>C	p.Asp526=	synonymous_variant	14/14	ENST00000291582.6	NP_000374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIRE	ENST00000291582.6 linkuse as main transcript	c.1578T>C	p.Asp526=	synonymous_variant	14/14	1	NM_000383.4	ENSP00000291582	P1	O43918-1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74726

AN:

151966

Hom.:

19354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.466

GnomAD3 exomes

AF:

0.459

AC:

114178

AN:

248750

Hom.:

27181

AF XY:

0.450

AC XY:

60801

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.652

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.659

Gnomad SAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.438

GnomAD4 exome

AF:

0.428

AC:

623919

AN:

1458944

Hom.:

135917

Cov.:

AF XY:

0.426

AC XY:

308893

AN XY:

725868

show subpopulations

Gnomad4 AFR exome

AF:

0.657

Gnomad4 AMR exome

AF:

0.499

Gnomad4 ASJ exome

AF:

0.444

Gnomad4 EAS exome

AF:

0.653

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.406

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.446

GnomAD4 genome

AF:

0.492

AC:

74819

AN:

152086

Hom.:

19394

Cov.:

AF XY:

0.494

AC XY:

36738

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.647

Gnomad4 AMR

AF:

0.497

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.667

Gnomad4 SAS

AF:

0.428

Gnomad4 FIN

AF:

0.410

Gnomad4 NFE

AF:

0.404

Gnomad4 OTH

AF:

0.470

Alfa

AF:

0.428

Hom.:

11837

Bravo

AF:

0.505

Asia WGS

AF:

0.509

AC:

1775

AN:

3478

EpiCase

AF:

0.418

EpiControl

AF:

0.412

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 26, 2017	- -

Polyglandular autoimmune syndrome, type 1

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.098

DANN

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over