21-33324192-G-T

Variant names:

• chr21-33324192-G-T
• rs17875752
• ENST00000687762.3:n.719C>A

Variant summary

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

The ENST00000687762.3(ENSG00000289238):​n.719C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,646 control chromosomes in the GnomAD database, including 11,059 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 (11059 hom., cov: 32)
• Consequence: ENSG00000289238 ENST00000687762.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 7 publications found

Genes affected

ENSG00000289238 (HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR1	NM_001384504.1	c.-578G>T		upstream_gene_variant			NP_001371433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289238	ENST00000687762.3	n.719C>A		non_coding_transcript_exon_variant	Exon 1 of 1
IFNAR1	ENST00000652450.2	c.-578G>T		upstream_gene_variant				ENSP00000498654.1
IFNAR1	ENST00000700080.1	c.-718G>T		upstream_gene_variant				ENSP00000514785.1
IFNAR1	ENST00000700084.1	c.-660G>T		upstream_gene_variant				ENSP00000514786.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57609 AN: 151528 Hom.: 11055 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.380 AC: 57628 AN: 151646 Hom.: 11059 Cov.: 32 AF XY: 0.379 AC XY: 28111 AN XY: 74122

African (AFR) AF: 0.320 AC: 13211 AN: 41338

American (AMR) AF: 0.411 AC: 6265 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1229 AN: 3466

East Asian (EAS) AF: 0.368 AC: 1902 AN: 5168

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4820

European-Finnish (FIN) AF: 0.401 AC: 4214 AN: 10508

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27498 AN: 67808

Other (OTH) AF: 0.403 AC: 844 AN: 2096

Alfa AF: 0.388 Hom.: 1445

Bravo AF: 0.378

Asia WGS AF: 0.363 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.28
PhyloP100		0.032
PromoterAI		-0.016	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17875752; hg19: chr21-34696497;