21-33358386-TAGAG-TAG

Variant names:

• chr21-33358386-TAG-T
• rs17875871
• NM_000629.3:c.*2843_*2844delGA

Variant summary

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

The NM_000629.3(IFNAR1):​c.*2843_*2844delGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 151,908 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 26)
• Consequence: IFNAR1 NM_000629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 7 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: STRONG Submitted by: 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	NM_000629.3	MANE Select	c.*2843_*2844delGA		3_prime_UTR	Exon 11 of 11	NP_000620.2
	IFNAR1	NM_001384498.1		c.*633_*634delGA		3_prime_UTR	Exon 12 of 12	NP_001371427.1
	IFNAR1	NM_001384503.1		c.*2843_*2844delGA		3_prime_UTR	Exon 11 of 11	NP_001371432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	ENST00000270139.8	TSL:1 MANE Select	c.*2843_*2844delGA		3_prime_UTR	Exon 11 of 11	ENSP00000270139.3
	IFNAR1	ENST00000651609.2		n.*4234_*4235delGA		non_coding_transcript_exon	Exon 11 of 11	ENSP00000498594.1
	IFNAR1	ENST00000652654.3		n.*3975_*3976delGA		non_coding_transcript_exon	Exon 10 of 10	ENSP00000498666.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151908 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151908 Hom.: 0 Cov.: 26 AF XY: 0.0000135 AC XY: 1 AN XY: 74204

African (AFR) AF: 0.0000726 AC: 3 AN: 41302

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 49

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10

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

Other links and lift over

dbSNP: rs17875871; hg19: chr21-34730692;