rs2243594

Positions:

• chr21-33335755-A-G
• chr21-33335755-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000629.3(IFNAR1):​c.200+108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 940,434 control chromosomes in the GnomAD database, including 76,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11188 hom., cov: 31)
  • Exomes 𝑓: 0.40 (65776 hom.)
• Consequence: IFNAR1 NM_000629.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 21-33335755-A-G is Benign according to our data. Variant chr21-33335755-A-G is described in ClinVar as [Benign]. Clinvar id is 2688255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR1	NM_000629.3	c.200+108A>G		intron_variant		ENST00000270139.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNAR1	ENST00000270139.8	c.200+108A>G		intron_variant		1	NM_000629.3	P4

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57828 AN: 151766 Hom.: 11184 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.404 AC: 318872 AN: 788550 Hom.: 65776 AF XY: 0.405 AC XY: 160968 AN XY: 397560

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.346

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.412

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.381 AC: 57847 AN: 151884 Hom.: 11188 Cov.: 31 AF XY: 0.380 AC XY: 28236 AN XY: 74254

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.402

Alfa AF: 0.372 Hom.: 1767

Bravo AF: 0.378

Asia WGS AF: 0.364 AC: 1264 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 29% of patients studied by a panel of primary immunodeficiencies. Number of patients: 28. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.1
DANN	Benign	0.84

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: rs2243594; hg19: chr21-34708061;