chr21-33358386-TAGAG-T

Position:

• chr21-33358386-TAGAG-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000629.3(IFNAR1):​c.*2841_*2844del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,946 control chromosomes in the GnomAD database, including 3,448 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3448 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: IFNAR1 NM_000629.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR1	NM_000629.3	c.*2841_*2844del		3_prime_UTR_variant	11/11	ENST00000270139.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNAR1	ENST00000270139.8	c.*2841_*2844del		3_prime_UTR_variant	11/11	1	NM_000629.3	P4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31294 AN: 151828 Hom.: 3440 Cov.: 26

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31311 AN: 151946 Hom.: 3448 Cov.: 26 AF XY: 0.206 AC XY: 15302 AN XY: 74270

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.221

Alfa AF: 0.0444 Hom.: 49

Bravo AF: 0.219

Asia WGS AF: 0.327 AC: 1137 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs17875871; hg19: chr21-34730692;