rs2226299

Variant names:

• chr21-33326619-A-G
• rs2226299
• NM_000629.3:c.76+1488A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-33326619-A-G
• chr21-33326619-A-T

Variant summary

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

The NM_000629.3(IFNAR1):​c.76+1488A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,132 control chromosomes in the GnomAD database, including 53,561 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 0.84 (53561 hom., cov: 31)
• Consequence: IFNAR1 NM_000629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 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.76+1488A>G		intron	N/A	NP_000620.2
	IFNAR1	NM_001384498.1		c.76+1488A>G		intron	N/A	NP_001371427.1
	IFNAR1	NM_001384503.1		c.76+1488A>G		intron	N/A	NP_001371432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	ENST00000270139.8	TSL:1 MANE Select	c.76+1488A>G		intron	N/A	ENSP00000270139.3
	IFNAR1	ENST00000703557.1		c.76+1488A>G		intron	N/A	ENSP00000515373.1
	IFNAR1	ENST00000652450.2		c.-132+1981A>G		intron	N/A	ENSP00000498654.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127044 AN: 152016 Hom.: 53494 Cov.: 31

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.836 AC: 127175 AN: 152132 Hom.: 53561 Cov.: 31 AF XY: 0.832 AC XY: 61831 AN XY: 74360

African (AFR) AF: 0.929 AC: 38589 AN: 41524

American (AMR) AF: 0.834 AC: 12764 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3470

East Asian (EAS) AF: 0.630 AC: 3257 AN: 5172

South Asian (SAS) AF: 0.763 AC: 3676 AN: 4818

European-Finnish (FIN) AF: 0.748 AC: 7888 AN: 10546

Middle Eastern (MID) AF: 0.894 AC: 261 AN: 292

European-Non Finnish (NFE) AF: 0.812 AC: 55211 AN: 68000

Other (OTH) AF: 0.844 AC: 1778 AN: 2106

Alfa AF: 0.806 Hom.: 7036

Bravo AF: 0.845

Asia WGS AF: 0.666 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		-1.6
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: rs2226299; hg19: chr21-34698924;