21-33358386-TAGAG-TAGAGAGAG

Variant names:

• chr21-33358386-T-TAGAG
• rs17875871
• NM_000629.3:c.*2841_*2844dupGAGA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000629.3(IFNAR1):​c.*2841_*2844dupGAGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 26)
• Consequence: IFNAR1 NM_000629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 0 publications found

Genes affected

IFNAR1 (HGNC:5432): (interferon alpha and beta receptor subunit 1) The protein encoded by this gene is a type I membrane protein that forms one of the two chains of a receptor for interferons alpha and beta. Binding and activation of the receptor stimulates Janus protein kinases, which in turn phosphorylate several proteins, including STAT1 and STAT2. The protein belongs to the type II cytokine receptor family and functions as an antiviral factor. [provided by RefSeq, Jul 2020]

IFNAR1 Gene-Disease associations (from GenCC):

• immunodeficiency 106, susceptibility to viral infections

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000629.3. 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
	IFNAR1	NM_000629.3	MANE Select	c.*2841_*2844dupGAGA		3_prime_UTR	Exon 11 of 11	NP_000620.2
	IFNAR1	NM_001384498.1		c.*631_*634dupGAGA		3_prime_UTR	Exon 12 of 12	NP_001371427.1
	IFNAR1	NM_001384503.1		c.*2841_*2844dupGAGA		3_prime_UTR	Exon 11 of 11	NP_001371432.1	A0A994J6F6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	ENST00000270139.8	TSL:1 MANE Select	c.*2841_*2844dupGAGA		3_prime_UTR	Exon 11 of 11	ENSP00000270139.3	P17181-1
	IFNAR1	ENST00000703557.1		c.*2841_*2844dupGAGA		3_prime_UTR	Exon 11 of 11	ENSP00000515373.1	A0A994J6F6
	IFNAR1	ENST00000652450.2		c.*2841_*2844dupGAGA		3_prime_UTR	Exon 11 of 11	ENSP00000498654.1	P17181-4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10

Splicing

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

Other links and lift over

dbSNP: rs17875871; hg19: chr21-34730692;