NM_000629.3:c.502G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000629.3(IFNAR1):c.502G>C(p.Val168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,610,902 control chromosomes in the GnomAD database, including 21,248 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V168V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.16 ( 2330 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18918 hom. )

Consequence

IFNAR1
NM_000629.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.195

Publications

72 publications found

Variant links:

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: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

IFNAR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042078197).

BP6

Variant 21-33343393-G-C is Benign according to our data. Variant chr21-33343393-G-C is described in ClinVar as Benign. ClinVar VariationId is 1170802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR1	NM_000629.3 link	c.502G>C	p.Val168Leu	missense_variant	Exon 4 of 11	ENST00000270139.8	NP_000620.2	P17181-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8 link	c.502G>C	p.Val168Leu	missense_variant	Exon 4 of 11	1	NM_000629.3	ENSP00000270139.3		P17181-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24799

AN:

152018

Hom.:

2322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.0887

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.180

GnomAD2 exomes

AF:

0.185

AC:

46302

AN:

250954

AF XY:

0.186

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.368

Gnomad FIN exome

AF:

0.0919

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.150

AC:

218622

AN:

1458768

Hom.:

18918

Cov.:

AF XY:

0.153

AC XY:

111246

AN XY:

725878

show subpopulations

African (AFR)

AF:

0.164

AC:

5490

AN:

33418

American (AMR)

AF:

0.251

AC:

11205

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

3799

AN:

26114

East Asian (EAS)

AF:

0.328

AC:

13013

AN:

39638

South Asian (SAS)

AF:

0.260

AC:

22350

AN:

86112

European-Finnish (FIN)

AF:

0.0952

AC:

5079

AN:

53370

Middle Eastern (MID)

AF:

0.260

AC:

1496

AN:

5750

European-Non Finnish (NFE)

AF:

0.131

AC:

145809

AN:

1109404

Other (OTH)

AF:

0.172

AC:

10381

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

8644

17288

25931

34575

43219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5440

10880

16320

21760

27200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.163

AC:

24812

AN:

152134

Hom.:

2330

Cov.:

AF XY:

0.165

AC XY:

12282

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.162

AC:

6719

AN:

41492

American (AMR)

AF:

0.234

AC:

3573

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

525

AN:

3470

East Asian (EAS)

AF:

0.375

AC:

1944

AN:

5188

South Asian (SAS)

AF:

0.278

AC:

1341

AN:

4826

European-Finnish (FIN)

AF:

0.0887

AC:

938

AN:

10570

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9244

AN:

67992

Other (OTH)

AF:

0.186

AC:

393

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1057

2115

3172

4230

5287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.146

Hom.:

587

Bravo

AF:

0.175

TwinsUK

AF:

0.132

AC:

488

ALSPAC

AF:

0.131

AC:

506

ESP6500AA

AF:

0.159

AC:

701

ESP6500EA

AF:

0.135

AC:

1159

ExAC

AF:

0.182

AC:

22091

Asia WGS

AF:

0.313

AC:

1087

AN:

3472

EpiCase

AF:

0.147

EpiControl

AF:

0.144

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.078

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.20

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

REVEL

Benign

0.092

Sift

Benign

0.12

Sift4G

Benign

0.23

Polyphen

0.76

Vest4

0.037

MPC

0.14

ClinPred

0.0037

GERP RS

0.84

Varity_R

0.36

gMVP

0.33

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over