rs2834202

Variant names:

• chr21-33358648-G-A
• rs2834202
• NM_000629.3:c.*3099G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000629.3(IFNAR1):​c.*3099G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 151,752 control chromosomes in the GnomAD database, including 45,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (45913 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: IFNAR1 NM_000629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	NM_000629.3	MANE Select	c.*3099G>A		3_prime_UTR	Exon 11 of 11	NP_000620.2
	IFNAR1	NM_001384498.1		c.*889G>A		3_prime_UTR	Exon 12 of 12	NP_001371427.1
	IFNAR1	NM_001384503.1		c.*3099G>A		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.*3099G>A		3_prime_UTR	Exon 11 of 11	ENSP00000270139.3	P17181-1
	IFNAR1	ENST00000703557.1		c.*3099G>A		3_prime_UTR	Exon 11 of 11	ENSP00000515373.1	A0A994J6F6
	IFNAR1	ENST00000652450.2		c.*3099G>A		3_prime_UTR	Exon 11 of 11	ENSP00000498654.1	P17181-4

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117528 AN: 151636 Hom.: 45870 Cov.: 30

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.777

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.775 AC: 117629 AN: 151752 Hom.: 45913 Cov.: 30 AF XY: 0.778 AC XY: 57706 AN XY: 74172

African (AFR) AF: 0.816 AC: 33815 AN: 41428

American (AMR) AF: 0.820 AC: 12498 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2703 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5149 AN: 5182

South Asian (SAS) AF: 0.867 AC: 4173 AN: 4812

European-Finnish (FIN) AF: 0.691 AC: 7195 AN: 10414

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49643 AN: 67906

Other (OTH) AF: 0.780 AC: 1639 AN: 2102

Alfa AF: 0.752 Hom.: 9619

Bravo AF: 0.789

Asia WGS AF: 0.933 AC: 3229 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.043
DANN	Benign	0.51
PhyloP100		-2.9
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: rs2834202; hg19: chr21-34730954;