rs1800525

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000383.4(AIRE):c.1095+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 1,545,422 control chromosomes in the GnomAD database, including 9,064 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1138 hom., cov: 33)

Exomes 𝑓: 0.095 ( 7926 hom. )

Consequence

AIRE
NM_000383.4 splice_region, intron

Scores

Splicing: ADA: 0.0002590

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.484

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

autoimmune polyendocrine syndrome type 1
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Ambry Genetics, Myriad Women’s Health, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
familial isolated hypoparathyroidism due to impaired PTH secretion
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

AIRE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 21-44292407-G-A is Benign according to our data. Variant chr21-44292407-G-A is described in ClinVar as Benign. ClinVar VariationId is 128329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIRE	NM_000383.4 link	c.1095+6G>A		splice_region_variant, intron_variant	Intron 9 of 13	ENST00000291582.6	NP_000374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIRE	ENST00000291582.6 link	c.1095+6G>A		splice_region_variant, intron_variant	Intron 9 of 13	1	NM_000383.4	ENSP00000291582.5

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16494

AN:

151784

Hom.:

1133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0925

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.0883

Gnomad OTH

AF:

0.112

GnomAD2 exomes

AF:

0.115

AC:

16809

AN:

146004

AF XY:

0.116

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0661

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.377

Gnomad FIN exome

AF:

0.0915

Gnomad NFE exome

AF:

0.0891

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.0946

AC:

131854

AN:

1393520

Hom.:

7926

Cov.:

AF XY:

0.0953

AC XY:

65510

AN XY:

687572

show subpopulations

African (AFR)

AF:

0.110

AC:

3489

AN:

31600

American (AMR)

AF:

0.0692

AC:

2476

AN:

35782

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3427

AN:

25134

East Asian (EAS)

AF:

0.354

AC:

12715

AN:

35894

South Asian (SAS)

AF:

0.109

AC:

8631

AN:

79158

European-Finnish (FIN)

AF:

0.0877

AC:

4191

AN:

47792

Middle Eastern (MID)

AF:

0.160

AC:

774

AN:

4832

European-Non Finnish (NFE)

AF:

0.0838

AC:

90148

AN:

1075604

Other (OTH)

AF:

0.104

AC:

6003

AN:

57724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

5713

11425

17138

22850

28563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3476

6952

10428

13904

17380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.109

AC:

16504

AN:

151902

Hom.:

1138

Cov.:

AF XY:

0.110

AC XY:

8198

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.110

AC:

4552

AN:

41410

American (AMR)

AF:

0.108

AC:

1648

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

504

AN:

3464

East Asian (EAS)

AF:

0.359

AC:

1831

AN:

5098

South Asian (SAS)

AF:

0.118

AC:

569

AN:

4822

European-Finnish (FIN)

AF:

0.0925

AC:

981

AN:

10608

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0883

AC:

5999

AN:

67904

Other (OTH)

AF:

0.116

AC:

245

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

709

1418

2127

2836

3545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0928

Hom.:

251

Bravo

AF:

0.111

Asia WGS

AF:

0.201

AC:

698

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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.

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Sep 21, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Polyglandular autoimmune syndrome, type 1

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

Dec 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19863576, 25402387, 23262341)

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Oct 11, 2017

Athena Diagnostics

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

-0.81

CADD

Benign

5.1

(source)

DANN

Benign

0.83

PhyloP100

0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over