21-33335755-A-T

Variant names:

• chr21-33335755-A-T
• rs2243594
• NM_000629.3:c.200+108A>T

Variant summary

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

The NM_000629.3(IFNAR1):​c.200+108A>T 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFNAR1 NM_000629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

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=-0.71).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	NM_000629.3	MANE Select	c.200+108A>T		intron	N/A	NP_000620.2
	IFNAR1	NM_001384498.1		c.200+108A>T		intron	N/A	NP_001371427.1
	IFNAR1	NM_001384503.1		c.200+108A>T		intron	N/A	NP_001371432.1	A0A994J6F6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	ENST00000270139.8	TSL:1 MANE Select	c.200+108A>T		intron	N/A	ENSP00000270139.3	P17181-1
	IFNAR1	ENST00000873010.1		c.200+108A>T		intron	N/A	ENSP00000543069.1
	IFNAR1	ENST00000703557.1		c.200+108A>T		intron	N/A	ENSP00000515373.1	A0A994J6F6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 790712 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 398684

African (AFR) AF: 0.00 AC: 0 AN: 17756

American (AMR) AF: 0.00 AC: 0 AN: 19488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14590

East Asian (EAS) AF: 0.00 AC: 0 AN: 31012

South Asian (SAS) AF: 0.00 AC: 0 AN: 40054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 587882

Other (OTH) AF: 0.00 AC: 0 AN: 35368

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1817

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.85
PhyloP100		0.012

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2243594;

hg19: chr21-34708061;