rs12483293

Positions:

• chr21-33344483-T-G
• chr21-33344483-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000629.3(IFNAR1):​c.674-763T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,440 control chromosomes in the GnomAD database, including 5,535 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 0.26 (5535 hom., cov: 32)
• Consequence: IFNAR1 NM_000629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNAR1	NM_000629.3	c.674-763T>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.674-763T>G		intron_variant		1	NM_000629.3	ENSP00000270139.3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38752 AN: 151322 Hom.: 5537 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.256 AC: 38754 AN: 151440 Hom.: 5535 Cov.: 32 AF XY: 0.262 AC XY: 19378 AN XY: 74018

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.257

Alfa AF: 0.269 Hom.: 9074

Bravo AF: 0.242

Asia WGS AF: 0.415 AC: 1442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.63

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: rs12483293; hg19: chr21-34716789;