21-33355024-G-A

Variant names:

• chr21-33355024-G-A
• rs1041868
• NM_000629.3:c.1441-292G>A

Variant summary

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

The NM_001384498.1(IFNAR1):​c.1441-292G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 150,746 control chromosomes in the GnomAD database, including 3,217 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 0.20 (3217 hom., cov: 31)
• Consequence: IFNAR1 NM_001384498.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384498.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	NM_000629.3	MANE Select	c.1441-292G>A		intron	N/A	NP_000620.2
	IFNAR1	NM_001384498.1		c.1441-292G>A		intron	N/A	NP_001371427.1
	IFNAR1	NM_001384503.1		c.1441-307G>A		intron	N/A	NP_001371432.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	ENST00000270139.8	TSL:1 MANE Select	c.1441-292G>A		intron	N/A	ENSP00000270139.3
	IFNAR1	ENST00000873010.1		c.1462-292G>A		intron	N/A	ENSP00000543069.1
	IFNAR1	ENST00000703557.1		c.1441-307G>A		intron	N/A	ENSP00000515373.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 29955 AN: 150670 Hom.: 3210 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.199 AC: 29974 AN: 150746 Hom.: 3217 Cov.: 31 AF XY: 0.200 AC XY: 14730 AN XY: 73514

African (AFR) AF: 0.196 AC: 8068 AN: 41102

American (AMR) AF: 0.264 AC: 4000 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3472

East Asian (EAS) AF: 0.385 AC: 1982 AN: 5142

South Asian (SAS) AF: 0.299 AC: 1432 AN: 4782

European-Finnish (FIN) AF: 0.129 AC: 1293 AN: 10020

Middle Eastern (MID) AF: 0.255 AC: 74 AN: 290

European-Non Finnish (NFE) AF: 0.176 AC: 11952 AN: 67790

Other (OTH) AF: 0.217 AC: 453 AN: 2092

Alfa AF: 0.187 Hom.: 4543

Bravo AF: 0.209

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.67
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1041868; hg19: chr21-34727330;