chr21-33344483-T-G

Variant names:

• chr21-33344483-T-G
• rs12483293
• NM_000629.3:c.674-763T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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 = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000629.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	NM_000629.3	MANE Select	c.674-763T>G		intron	N/A	NP_000620.2
	IFNAR1	NM_001384498.1		c.674-763T>G		intron	N/A	NP_001371427.1
	IFNAR1	NM_001384503.1		c.674-763T>G		intron	N/A	NP_001371432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	ENST00000270139.8	TSL:1 MANE Select	c.674-763T>G		intron	N/A	ENSP00000270139.3
	IFNAR1	ENST00000703557.1		c.674-763T>G		intron	N/A	ENSP00000515373.1
	IFNAR1	ENST00000652450.2		c.467-763T>G		intron	N/A	ENSP00000498654.1

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

African (AFR) AF: 0.157 AC: 6490 AN: 41458

American (AMR) AF: 0.236 AC: 3596 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 806 AN: 3448

East Asian (EAS) AF: 0.381 AC: 1963 AN: 5148

South Asian (SAS) AF: 0.367 AC: 1768 AN: 4812

European-Finnish (FIN) AF: 0.365 AC: 3812 AN: 10456

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19427 AN: 67588

Other (OTH) AF: 0.257 AC: 540 AN: 2104

Alfa AF: 0.275 Hom.: 21165

Bravo AF: 0.242

Asia WGS AF: 0.415 AC: 1442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-0.040
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: rs12483293; hg19: chr21-34716789;