rs1041868

Variant names:

• chr21-33355024-G-A
• rs1041868
• NM_000629.3:c.1441-292G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-33355024-G-A
• chr21-33355024-G-C

Variant summary

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

The NM_000629.3(IFNAR1):​c.1441-292G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 150,746 control chromosomes in the GnomAD database, including 3,217 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 0.20 (3217 hom., cov: 31)
• Consequence: IFNAR1 NM_000629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR1	NM_000629.3	c.1441-292G>A		intron_variant	Intron 10 of 10	ENST00000270139.8	NP_000620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8	c.1441-292G>A		intron_variant	Intron 10 of 10	1	NM_000629.3	ENSP00000270139.3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 29955 AN: 150670 Hom.: 3210 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.199 AC: 29974 AN: 150746 Hom.: 3217 Cov.: 31 AF XY: 0.200 AC XY: 14730 AN XY: 73514

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.217

Alfa AF: 0.186 Hom.: 3456

Bravo AF: 0.209

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.67

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: rs1041868; hg19: chr21-34727330;