Genetic Variant IFNAR1:c.200+108A>T (chr21-33335755-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0120

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR1	NM_000629.3 link	c.200+108A>T		intron_variant	Intron 2 of 10	ENST00000270139.8	NP_000620.2	P17181-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8 link	c.200+108A>T		intron_variant	Intron 2 of 10	1	NM_000629.3	ENSP00000270139.3		P17181-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

790712

Hom.:

AF XY:

0.00

AC XY:

AN XY:

398684

African (AFR)

AF:

0.00

AC:

AN:

17756

American (AMR)

AF:

0.00

AC:

AN:

19488

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14590

East Asian (EAS)

AF:

0.00

AC:

AN:

31012

South Asian (SAS)

AF:

0.00

AC:

AN:

40054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

587882

Other (OTH)

AF:

0.00

AC:

AN:

35368

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1817

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.7

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over