chr21-33358648-G-A

Position:

• chr21-33358648-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000629.3(IFNAR1):​c.*3099G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 151,752 control chromosomes in the GnomAD database, including 45,913 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 0.78 (45913 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: IFNAR1 NM_000629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNAR1	NM_000629.3	c.*3099G>A		3_prime_UTR_variant	11/11	ENST00000270139.8	NP_000620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8	c.*3099G>A		3_prime_UTR_variant	11/11	1	NM_000629.3	ENSP00000270139.3

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117528 AN: 151636 Hom.: 45870 Cov.: 30

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.777

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.775 AC: 117629 AN: 151752 Hom.: 45913 Cov.: 30 AF XY: 0.778 AC XY: 57706 AN XY: 74172

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.780

Alfa AF: 0.752 Hom.: 9619

Bravo AF: 0.789

Asia WGS AF: 0.933 AC: 3229 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.043
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs2834202; hg19: chr21-34730954;