Genetic Variant ENSG00000289238:n.509G>C (chr21-33324402-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000687762.3(ENSG00000289238):n.509G>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 0.381 in 152,988 control chromosomes in the GnomAD database, including 11,266 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 0.38 ( 11153 hom., cov: 32)

Exomes 𝑓: 0.46 ( 113 hom. )

Consequence

ENSG00000289238
ENST00000687762.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

17 publications found

Variant links:

COSMIC-nc: COSV54253597

Genes affected

ENSG00000289238 (HGNC:):

ENSG00000289238 links:

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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNAR1	NM_001384504.1 link	c.-368C>G		5_prime_UTR_variant	Exon 1 of 11		NP_001371433.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
ENSG00000289238	ENST00000687762.3 link	n.509G>C	non_coding_transcript_exon_variant	Exon 1 of 1
IFNAR1	ENST00000652450.2 link	c.-368C>G	5_prime_UTR_variant	Exon 1 of 11	ENSP00000498654.1	P17181-4
IFNAR1	ENST00000700080.1 link	c.-508C>G	5_prime_UTR_variant	Exon 1 of 11	ENSP00000514785.1	P17181-4

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57768

AN:

151926

Hom.:

11149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.400

GnomAD4 exome

AF:

0.458

AC:

432

AN:

944

Hom.:

113

AF XY:

0.455

AC XY:

337

AN XY:

740

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0833

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.426

AC:

AN:

108

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.481

AC:

352

AN:

732

Other (OTH)

AF:

0.452

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.380

AC:

57788

AN:

152044

Hom.:

11153

Cov.:

AF XY:

0.379

AC XY:

28196

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.318

AC:

13183

AN:

41480

American (AMR)

AF:

0.411

AC:

6282

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

1234

AN:

3470

East Asian (EAS)

AF:

0.369

AC:

1906

AN:

5166

South Asian (SAS)

AF:

0.405

AC:

1955

AN:

4822

European-Finnish (FIN)

AF:

0.402

AC:

4242

AN:

10558

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.406

AC:

27619

AN:

67970

Other (OTH)

AF:

0.403

AC:

848

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1840

3679

5519

7358

9198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.269

Hom.:

746

Bravo

AF:

0.378

Asia WGS

AF:

0.365

AC:

1268

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

9.0

(source)

DANN

Benign

0.58

PhyloP100

1.3

PromoterAI

-0.039

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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