rs1012334

Positions:

• chr21-33341445-A-T
• chr21-33341445-A-C

Variant summary

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

The NM_000629.3(IFNAR1):​c.376+271A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,034 control chromosomes in the GnomAD database, including 25,006 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 0.56 (25006 hom., cov: 32)
• Consequence: IFNAR1 NM_000629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR1	NM_000629.3	c.376+271A>T		intron_variant		ENST00000270139.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNAR1	ENST00000270139.8	c.376+271A>T		intron_variant		1	NM_000629.3	P4

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84449 AN: 151916 Hom.: 24951 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.556 AC: 84566 AN: 152034 Hom.: 25006 Cov.: 32 AF XY: 0.550 AC XY: 40860 AN XY: 74316

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.553

Alfa AF: 0.505 Hom.: 2705

Bravo AF: 0.569

Asia WGS AF: 0.449 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.75
DANN	Benign	0.49

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: rs1012334; hg19: chr21-34713751;