rs2226299

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNAR1	NM_000629.3	c.76+1488A>G		intron_variant		ENST00000270139.8	NP_000620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8	c.76+1488A>G		intron_variant		1	NM_000629.3	ENSP00000270139	P4

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

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.844

Alfa AF: 0.801 Hom.: 6698

Bravo AF: 0.845

Asia WGS AF: 0.666 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.8
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs2226299; hg19: chr21-34698924;