21-33358386-TAGAG-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000629.3(IFNAR1):​c.*2841_*2844delGAGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,946 control chromosomes in the GnomAD database, including 3,448 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3448 hom., cov: 26)
  • Failed GnomAD Quality Control
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

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.*2841_*2844delGAGA		3_prime_UTR	Exon 11 of 11	NP_000620.2
	IFNAR1	NM_001384498.1		c.*631_*634delGAGA		3_prime_UTR	Exon 12 of 12	NP_001371427.1
	IFNAR1	NM_001384503.1		c.*2841_*2844delGAGA		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.*2841_*2844delGAGA		3_prime_UTR	Exon 11 of 11	ENSP00000270139.3
	IFNAR1	ENST00000651609.2		n.*4232_*4235delGAGA		non_coding_transcript_exon	Exon 11 of 11	ENSP00000498594.1
	IFNAR1	ENST00000652654.3		n.*3973_*3976delGAGA		non_coding_transcript_exon	Exon 10 of 10	ENSP00000498666.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31294 AN: 151828 Hom.: 3440 Cov.: 26

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.206 AC: 31311 AN: 151946 Hom.: 3448 Cov.: 26 AF XY: 0.206 AC XY: 15302 AN XY: 74270

African (AFR) AF: 0.226 AC: 9373 AN: 41392

American (AMR) AF: 0.263 AC: 4003 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1972 AN: 5166

South Asian (SAS) AF: 0.299 AC: 1444 AN: 4822

European-Finnish (FIN) AF: 0.122 AC: 1292 AN: 10558

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11967 AN: 67972

Other (OTH) AF: 0.221 AC: 467 AN: 2114

Alfa AF: 0.0444 Hom.: 49

Bravo AF: 0.219

Asia WGS AF: 0.327 AC: 1137 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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;