rs914142

Positions:

• chr21-33353501-G-A
• chr21-33353501-G-T

Variant summary

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

The NM_000629.3(IFNAR1):​c.1295-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 534,824 control chromosomes in the GnomAD database, including 159,019 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 (46118 hom., cov: 32)
  • Exomes 𝑓: 0.76 (112901 hom.)
• Consequence: IFNAR1 NM_000629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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 (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNAR1	NM_000629.3	c.1295-137G>A		intron_variant		ENST00000270139.8	NP_000620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8	c.1295-137G>A		intron_variant		1	NM_000629.3	ENSP00000270139	P4

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117922 AN: 152016 Hom.: 46074 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.778

GnomAD4 exome AF: 0.765 AC: 292749 AN: 382690 Hom.: 112901 AF XY: 0.769 AC XY: 154427 AN XY: 200918

Gnomad4 AFR exome AF: 0.814

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.786

Gnomad4 EAS exome AF: 0.987

Gnomad4 SAS exome AF: 0.850

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.734

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.776 AC: 118025 AN: 152134 Hom.: 46118 Cov.: 32 AF XY: 0.779 AC XY: 57897 AN XY: 74366

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.781

Alfa AF: 0.748 Hom.: 85497

Bravo AF: 0.789

Asia WGS AF: 0.934 AC: 3246 AN: 3476

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	0.81

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: rs914142; hg19: chr21-34725807;