chr21-33341701-G-C

Variant names:

• chr21-33341701-G-C
• rs1012335
• NM_000629.3:c.376+527G>C

Variant summary

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

The NM_000629.3(IFNAR1):​c.376+527G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,262 control chromosomes in the GnomAD database, including 11,104 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 0.38 (11104 hom., cov: 31)
• Consequence: IFNAR1 NM_000629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR1	NM_000629.3	c.376+527G>C		intron_variant	Intron 3 of 10	ENST00000270139.8	NP_000620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8	c.376+527G>C		intron_variant	Intron 3 of 10	1	NM_000629.3	ENSP00000270139.3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57658 AN: 151144 Hom.: 11095 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.381 AC: 57687 AN: 151262 Hom.: 11104 Cov.: 31 AF XY: 0.382 AC XY: 28175 AN XY: 73814

African (AFR) AF: 0.321 AC: 13227 AN: 41184

American (AMR) AF: 0.407 AC: 6189 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3466

East Asian (EAS) AF: 0.398 AC: 2053 AN: 5160

South Asian (SAS) AF: 0.408 AC: 1964 AN: 4808

European-Finnish (FIN) AF: 0.404 AC: 4173 AN: 10322

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.404 AC: 27423 AN: 67812

Other (OTH) AF: 0.401 AC: 840 AN: 2094

Alfa AF: 0.375 Hom.: 1345

Bravo AF: 0.377

Asia WGS AF: 0.377 AC: 1309 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1012335; hg19: chr21-34714007;