rs2843710

Positions:

• chr21-33324402-C-G
• chr21-33324402-C-A
• chr21-33324402-C-T

Variant summary

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

The ENST00000687762.2(ENSG00000289238):​n.471G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,988 control chromosomes in the GnomAD database, including 11,266 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 0.38 (11153 hom., cov: 32)
  • Exomes 𝑓: 0.46 (113 hom.)
• Consequence: ENST00000687762.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

Genes affected

(HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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	Protein	UniProt
IFNAR1	NM_001384504.1	c.-368C>G		5_prime_UTR_variant	1/11		NP_001371433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000687762.2	n.471G>C		non_coding_transcript_exon_variant	1/1
IFNAR1	ENST00000652450.2	c.-368C>G		5_prime_UTR_variant	1/11			ENSP00000498654
IFNAR1	ENST00000700080.1	c.-508C>G		5_prime_UTR_variant	1/11			ENSP00000514785
IFNAR1	ENST00000700084.1	c.-450C>G		5_prime_UTR_variant	1/8			ENSP00000514786

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57768 AN: 151926 Hom.: 11149 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.458 AC: 432 AN: 944 Hom.: 113 AF XY: 0.455 AC XY: 337 AN XY: 740

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0833

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.380 AC: 57788 AN: 152044 Hom.: 11153 Cov.: 32 AF XY: 0.379 AC XY: 28196 AN XY: 74308

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.403

Alfa AF: 0.269 Hom.: 746

Bravo AF: 0.378

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2843710; hg19: chr21-34696707; COSMIC: COSV54253597;