Genetic Variant IFNAR1:n.-97T>C (chr21-33324959-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000652654.3(IFNAR1):n.-97T>C variant causes a non coding transcript exon 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
ENST00000652654.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

Publications

23 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:

ENSG00000289238 (HGNC:):

ENSG00000289238 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IFNAR1	NM_000629.3 link	c.-97T>C		upstream_gene_variant		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.-97T>C		upstream_gene_variant		1	NM_000629.3	ENSP00000270139.3		P17181-1

Frequencies

GnomAD3 genomes

AF:

0.789

AC:

118887

AN:

150640

Hom.:

47777

Cov.:

show subpopulations

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.:

AF XY:

0.744

AC XY:

343081

AN XY:

461334

show subpopulations

African (AFR)

AF:

0.955

AC:

21699

AN:

22732

American (AMR)

AF:

0.687

AC:

22700

AN:

33036

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

12771

AN:

20246

East Asian (EAS)

AF:

0.779

AC:

25853

AN:

33186

South Asian (SAS)

AF:

0.818

AC:

53681

AN:

65632

European-Finnish (FIN)

AF:

0.785

AC:

33710

AN:

42964

Middle Eastern (MID)

AF:

0.725

AC:

3029

AN:

4180

European-Non Finnish (NFE)

AF:

0.727

AC:

472323

AN:

649620

Other (OTH)

AF:

0.756

AC:

31582

AN:

41756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

8594

17188

25781

34375

42969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9674

19348

29022

38696

48370

<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:

0.789

AC:

118989

AN:

150758

Hom.:

47825

Cov.:

AF XY:

0.790

AC XY:

58125

AN XY:

73608

show subpopulations

African (AFR)

AF:

0.946

AC:

38847

AN:

41054

American (AMR)

AF:

0.710

AC:

10782

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2164

AN:

3456

East Asian (EAS)

AF:

0.755

AC:

3835

AN:

5082

South Asian (SAS)

AF:

0.823

AC:

3906

AN:

4748

European-Finnish (FIN)

AF:

0.786

AC:

8166

AN:

10384

Middle Eastern (MID)

AF:

0.767

AC:

224

AN:

292

European-Non Finnish (NFE)

AF:

0.722

AC:

48770

AN:

67580

Other (OTH)

AF:

0.771

AC:

1603

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1146

2292

3438

4584

5730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.746

Hom.:

92464

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

(source)

DANN

Benign

0.44

PhyloP100

-0.23

PromoterAI

0.77

Over-expression

(source)

Mutation Taster

=300/0

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

Computational scores

Splicing

Publications

Other links and lift over