chr21-33324959-T-C

Position:

• chr21-33324959-T-C

Variant summary

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

The ENST00000703557.1(IFNAR1):​c.-97T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 1,064,110 control chromosomes in the GnomAD database, including 300,573 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 0.79 (47825 hom., cov: 29)
  • Exomes 𝑓: 0.74 (252748 hom.)
• Consequence: IFNAR1 ENST00000703557.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNAR1	NM_000629.3			upstream_gene_variant		ENST00000270139.8	NP_000620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8			upstream_gene_variant		1	NM_000629.3	ENSP00000270139	P4

Frequencies

GnomAD3 genomes AF: 0.789 AC: 118887 AN: 150640 Hom.: 47777 Cov.: 29

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.768

GnomAD4 exome AF: 0.742 AC: 677348 AN: 913352 Hom.: 252748 Cov.: 12 AF XY: 0.744 AC XY: 343081 AN XY: 461334

Gnomad4 AFR exome AF: 0.955

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.779

Gnomad4 SAS exome AF: 0.818

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.727

Gnomad4 OTH exome AF: 0.756

GnomAD4 genome AF: 0.789 AC: 118989 AN: 150758 Hom.: 47825 Cov.: 29 AF XY: 0.790 AC XY: 58125 AN XY: 73608

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.771

Alfa AF: 0.727 Hom.: 46923

Bravo AF: 0.791

Asia WGS AF: 0.834 AC: 2902 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	10
DANN	Benign	0.44

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: rs2850015; hg19: chr21-34697264; COSMIC: COSV54253610; COSMIC: COSV54253610;