rs11910214

Variant names:

• chr21-44287550-C-A
• NM_000383.4:c.497C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-44287550-C-A
• chr21-44287550-C-G
• chr21-44287550-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000383.4(AIRE):​c.497C>A​(p.Pro166Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: AIRE NM_000383.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23787206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIRE	NM_000383.4	c.497C>A	p.Pro166Gln	missense_variant	Exon 4 of 14	ENST00000291582.6	NP_000374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIRE	ENST00000291582.6	c.497C>A	p.Pro166Gln	missense_variant	Exon 4 of 14	1	NM_000383.4	ENSP00000291582.5
AIRE	ENST00000527919.5	n.1041C>A		non_coding_transcript_exon_variant	Exon 3 of 14	2
AIRE	ENST00000530812.5	n.1049C>A		non_coding_transcript_exon_variant	Exon 3 of 12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406990 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 694682

Gnomad4 AFR exome AF: 0.0000310

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	0.0018	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	4.3
DANN	Benign	0.95
DEOGEN2	Uncertain	0.70	D
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	0.040	D
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.26
Sift	Benign	0.058	T
Sift4G	Benign	0.065	T
Polyphen		0.90	P
Vest4		0.071
MutPred		0.21		Loss of glycosylation at P166 (P = 0.0166);
MVP		0.99
MPC		0.12
ClinPred		0.59	D
GERP RS		1.4
Varity_R		0.071
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-45707433;