rs940699652

Variant names:

• chr21-33325076-C-T
• rs940699652
• NM_000629.3:c.21C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000629.3(IFNAR1):​c.21C>T​(p.Gly7Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IFNAR1 NM_000629.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.487
• Publications: 0 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: ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000289238 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP6: Variant 21-33325076-C-T is Benign according to our data. Variant chr21-33325076-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1979265.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.487 with no splicing effect.

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.21C>T	p.Gly7Gly	synonymous	Exon 1 of 11	NP_000620.2
	IFNAR1	NM_001384498.1		c.21C>T	p.Gly7Gly	synonymous	Exon 1 of 12	NP_001371427.1
	IFNAR1	NM_001384503.1		c.21C>T	p.Gly7Gly	synonymous	Exon 1 of 11	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.21C>T	p.Gly7Gly	synonymous	Exon 1 of 11	ENSP00000270139.3	P17181-1
	IFNAR1	ENST00000873010.1		c.21C>T	p.Gly7Gly	synonymous	Exon 1 of 12	ENSP00000543069.1
	IFNAR1	ENST00000703557.1		c.21C>T	p.Gly7Gly	synonymous	Exon 1 of 11	ENSP00000515373.1	A0A994J6F6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000419 AC: 1 AN: 238642 AF XY: 0.00000769

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000931

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456774 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724452

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110508

Other (OTH) AF: 0.00 AC: 0 AN: 60118

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	10
DANN	Benign	0.96
PhyloP100		-0.49
PromoterAI		-0.0045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs940699652; hg19: chr21-34697381;