dbSNP rs8178435: IFNAR2-IL10RB:c.710-2682A>G (chr21-33265712-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000433395.7(IFNAR2-IL10RB):c.710-2682A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 278,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

IFNAR2-IL10RB
ENST00000433395.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.590

Publications

2 publications found

Variant links:

Genes affected

IFNAR2-IL10RB (HGNC:):

IFNAR2-IL10RB links:

IL10RB-DT (HGNC:44303): (IL10RB divergent transcript)

IL10RB-DT links:

IFNAR2 (HGNC:5433): (interferon alpha and beta receptor subunit 2) 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. Mutations in this gene are associated with Immunodeficiency 45. [provided by RefSeq, Jul 2020]

IFNAR2 Gene-Disease associations (from GenCC):

immunodeficiency 45
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

IFNAR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR2	NM_001289125.3 link	c.*2212A>G		downstream_gene_variant		ENST00000342136.9	NP_001276054.1	P48551-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNAR2-IL10RB	ENST00000433395.7 link	c.710-2682A>G		intron_variant	Intron 7 of 12	5		ENSP00000388223.3		H0Y3Z8
IFNAR2	ENST00000342136.9 link	c.*2212A>G		downstream_gene_variant		1	NM_001289125.3	ENSP00000343957.5		P48551-1

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

333

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00764

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.000150

AC:

AN:

126490

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

71502

show subpopulations

African (AFR)

AF:

0.00591

AC:

AN:

1692

American (AMR)

AF:

0.000620

AC:

AN:

4836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2344

East Asian (EAS)

AF:

0.00

AC:

AN:

2678

South Asian (SAS)

AF:

0.0000319

AC:

AN:

31360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

728

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

70304

Other (OTH)

AF:

0.000819

AC:

AN:

6104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00220

AC:

334

AN:

152130

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00764

AC:

317

AN:

41496

American (AMR)

AF:

0.000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68004

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00215

Hom.:

Bravo

AF:

0.00266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

7.9

(source)

DANN

Benign

0.39

PhyloP100

0.59

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