rs2243594

Variant names:

• chr21-33335755-A-G
• rs2243594
• NM_000629.3:c.200+108A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

IFNAR1 Gene-Disease associations (from GenCC):

• immunodeficiency 106, susceptibility to viral infections

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000629.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	NM_000629.3	MANE Select	c.200+108A>G		intron	N/A	NP_000620.2
	IFNAR1	NM_001384498.1		c.200+108A>G		intron	N/A	NP_001371427.1
	IFNAR1	NM_001384503.1		c.200+108A>G		intron	N/A	NP_001371432.1	A0A994J6F6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR1	ENST00000270139.8	TSL:1 MANE Select	c.200+108A>G		intron	N/A	ENSP00000270139.3	P17181-1
	IFNAR1	ENST00000873010.1		c.200+108A>G		intron	N/A	ENSP00000543069.1
	IFNAR1	ENST00000703557.1		c.200+108A>G		intron	N/A	ENSP00000515373.1	A0A994J6F6

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

African (AFR) AF: 0.324 AC: 5744 AN: 17710

American (AMR) AF: 0.409 AC: 7950 AN: 19438

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 5028 AN: 14552

East Asian (EAS) AF: 0.325 AC: 10065 AN: 30936

South Asian (SAS) AF: 0.412 AC: 16436 AN: 39920

European-Finnish (FIN) AF: 0.405 AC: 16667 AN: 41202

Middle Eastern (MID) AF: 0.443 AC: 1429 AN: 3228

European-Non Finnish (NFE) AF: 0.411 AC: 241159 AN: 586290

Other (OTH) AF: 0.408 AC: 14394 AN: 35274

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

African (AFR) AF: 0.320 AC: 13257 AN: 41422

American (AMR) AF: 0.411 AC: 6273 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1915 AN: 5176

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4818

European-Finnish (FIN) AF: 0.402 AC: 4228 AN: 10506

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27619 AN: 67922

Other (OTH) AF: 0.402 AC: 850 AN: 2114

Alfa AF: 0.372 Hom.: 1817

Bravo AF: 0.378

Asia WGS AF: 0.364 AC: 1264 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.1
DANN	Benign	0.84
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2243594;

hg19: chr21-34708061;