Genetic Variant ENST00000652654.3:n.-97T>A (chr21-33324807-G-A) – 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 ENST00000652654.3(IFNAR1):n.-249G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 393,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

IFNAR1
ENST00000652654.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

Publications

0 publications found

Variant links:

Genes affected

ENSG00000289238 (HGNC:):

ENSG00000289238 links:

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)

IFNAR1 links:

Genome browser will be placed here

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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR1	NM_000629.3 link	c.-249G>A		upstream_gene_variant		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.-249G>A		upstream_gene_variant		1	NM_000629.3	ENSP00000270139.3		P17181-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000254

AC:

AN:

393844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

206632

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11294

American (AMR)

AF:

0.00

AC:

AN:

16154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12470

East Asian (EAS)

AF:

0.00

AC:

AN:

27940

South Asian (SAS)

AF:

0.0000263

AC:

AN:

37956

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

235846

Other (OTH)

AF:

0.00

AC:

AN:

23156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.4

(source)

DANN

Benign

0.77

PhyloP100

-1.3

PromoterAI

-0.018

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over