chr21-33324959-T-G

Variant names:

• chr21-33324959-T-G
• rs2850015
• ENST00000703557.1:c.-97T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384504.1(IFNAR1):​c.-132+321T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFNAR1 NM_001384504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 23 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: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000289238 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384504.1. 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_001384504.1		c.-132+321T>G		intron	N/A	NP_001371433.1	P17181-4
	IFNAR1	NM_000629.3	MANE Select	c.-97T>G		upstream_gene	N/A	NP_000620.2
	IFNAR1	NM_001384498.1		c.-97T>G		upstream_gene	N/A	NP_001371427.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	ENST00000703557.1		c.-97T>G		5_prime_UTR	Exon 1 of 11	ENSP00000515373.1	A0A994J6F6
	IFNAR1	ENST00000442071.3	TSL:3	c.-97T>G		5_prime_UTR	Exon 1 of 9	ENSP00000400161.3	C9J114
	IFNAR1	ENST00000703561.1		c.-97T>G		5_prime_UTR	Exon 1 of 9	ENSP00000515377.1	A0A994J3P7

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 914762 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 462020

African (AFR) AF: 0.00 AC: 0 AN: 22738

American (AMR) AF: 0.00 AC: 0 AN: 33060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20274

East Asian (EAS) AF: 0.00 AC: 0 AN: 33194

South Asian (SAS) AF: 0.00 AC: 0 AN: 65688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4184

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 650786

Other (OTH) AF: 0.00 AC: 0 AN: 41816

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 92464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.2
DANN	Benign	0.43
PhyloP100		-0.23
PromoterAI		-0.34	Neutral

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: rs2850015; hg19: chr21-34697264;