Variant chr21-33335502-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000629.3(IFNAR1):c.77-22T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,444,442 control chromosomes in the GnomAD database, including 109,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.38 ( 11183 hom., cov: 31)

Exomes 𝑓: 0.39 ( 98791 hom. )

Consequence

IFNAR1
NM_000629.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.54

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 21-33335502-T-G is Benign according to our data. Variant chr21-33335502-T-G is described in ClinVar as [Benign]. Clinvar id is 2688073.Status of the report is criteria_provided_single_submitter, 1 stars.

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/exons	MANE	Protein	UniProt
IFNAR1	NM_000629.3 linkuse as main transcript	c.77-22T>G		intron_variant		ENST00000270139.8	NP_000620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNAR1	ENST00000270139.8 linkuse as main transcript	c.77-22T>G		intron_variant		1	NM_000629.3	ENSP00000270139	P4	P17181-1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57830

AN:

151900

Hom.:

11179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.399

GnomAD3 exomes

AF:

0.394

AC:

90086

AN:

228704

Hom.:

17700

AF XY:

0.396

AC XY:

49090

AN XY:

123868

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.360

Gnomad SAS exome

AF:

0.417

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.408

GnomAD4 exome

AF:

0.389

AC:

502273

AN:

1292424

Hom.:

98791

Cov.:

AF XY:

0.390

AC XY:

253276

AN XY:

649228

show subpopulations

Gnomad4 AFR exome

AF:

0.314

Gnomad4 AMR exome

AF:

0.401

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.328

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.394

GnomAD4 genome

AF:

0.381

AC:

57849

AN:

152018

Hom.:

11183

Cov.:

AF XY:

0.380

AC XY:

28231

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.320

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.370

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.403

Gnomad4 NFE

AF:

0.406

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.389

Hom.:

2159

Bravo

AF:

0.378

Asia WGS

AF:

0.365

AC:

1271

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 57. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.77

BranchPoint Hunter

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over