dbSNP rs914142: IFNAR1:c.1295-137G>A (chr21-33353501-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000629.3(IFNAR1):c.1295-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 534,824 control chromosomes in the GnomAD database, including 159,019 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 0.78 ( 46118 hom., cov: 32)

Exomes 𝑓: 0.76 ( 112901 hom. )

Consequence

IFNAR1
NM_000629.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.43

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR1	NM_000629.3 link	c.1295-137G>A		intron_variant	Intron 9 of 10	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.1295-137G>A		intron_variant	Intron 9 of 10	1	NM_000629.3	ENSP00000270139.3		P17181-1

Frequencies

GnomAD3 genomes

AF:

0.776

AC:

117922

AN:

152016

Hom.:

46074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.823

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.870

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.732

Gnomad OTH

AF:

0.778

GnomAD4 exome

AF:

0.765

AC:

292749

AN:

382690

Hom.:

112901

AF XY:

0.769

AC XY:

154427

AN XY:

200918

show subpopulations

African (AFR)

AF:

0.814

AC:

6800

AN:

8350

American (AMR)

AF:

0.847

AC:

8091

AN:

9554

Ashkenazi Jewish (ASJ)

AF:

0.786

AC:

9393

AN:

11954

East Asian (EAS)

AF:

0.987

AC:

23609

AN:

23918

South Asian (SAS)

AF:

0.850

AC:

25994

AN:

30586

European-Finnish (FIN)

AF:

0.700

AC:

21281

AN:

30380

Middle Eastern (MID)

AF:

0.805

AC:

1425

AN:

1770

European-Non Finnish (NFE)

AF:

0.734

AC:

178818

AN:

243576

Other (OTH)

AF:

0.767

AC:

17338

AN:

22602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3110

6220

9330

12440

15550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.776

AC:

118025

AN:

152134

Hom.:

46118

Cov.:

AF XY:

0.779

AC XY:

57897

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.816

AC:

33879

AN:

41502

American (AMR)

AF:

0.823

AC:

12585

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.778

AC:

2699

AN:

3468

East Asian (EAS)

AF:

0.994

AC:

5159

AN:

5192

South Asian (SAS)

AF:

0.870

AC:

4194

AN:

4822

European-Finnish (FIN)

AF:

0.691

AC:

7298

AN:

10556

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.732

AC:

49744

AN:

67988

Other (OTH)

AF:

0.781

AC:

1648

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1335

2670

4004

5339

6674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.754

Hom.:

137460

Bravo

AF:

0.789

Asia WGS

AF:

0.934

AC:

3246

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.75

(source)

DANN

Benign

0.81

PhyloP100

-2.4

Mutation Taster

=100/0

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