21-44285930-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000383.4(AIRE):c.-77C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,433,534 control chromosomes in the GnomAD database, including 278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (180 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (98 hom.)
• Consequence: AIRE NM_000383.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.68

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 21-44285930-C-A is Benign according to our data. Variant chr21-44285930-C-A is described in ClinVar as [Benign]. Clinvar id is 1283137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIRE	NM_000383.4	c.-77C>A		5_prime_UTR_variant	1/14	ENST00000291582.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIRE	ENST00000291582.6	c.-77C>A		5_prime_UTR_variant	1/14	1	NM_000383.4	P1
AIRE	ENST00000527919.5	n.85C>A		non_coding_transcript_exon_variant	1/14	2
AIRE	ENST00000530812.5	n.93C>A		non_coding_transcript_exon_variant	1/12	2

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3945 AN: 152050 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00212 AC: 2715 AN: 1281376 Hom.: 98 Cov.: 24 AF XY: 0.00175 AC XY: 1111 AN XY: 634248

Gnomad4 AFR exome AF: 0.0877

Gnomad4 AMR exome AF: 0.00486

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000343

Gnomad4 SAS exome AF: 0.0000824

Gnomad4 FIN exome AF: 0.000274

Gnomad4 NFE exome AF: 0.0000819

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.0260 AC: 3950 AN: 152158 Hom.: 180 Cov.: 32 AF XY: 0.0254 AC XY: 1893 AN XY: 74406

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0205 Hom.: 15

Bravo AF: 0.0299

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	4.6
Dann	Benign	0.90

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

Other links and lift over

dbSNP: rs150767556; hg19: chr21-45705813;