Variant 21-33432659-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005534.4(IFNGR2):c.722-55T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,579,122 control chromosomes in the GnomAD database, including 424,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45996 hom., cov: 31)

Exomes 𝑓: 0.73 ( 378207 hom. )

Consequence

IFNGR2
NM_005534.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

IFNGR2 (HGNC:5440): (interferon gamma receptor 2) This gene (IFNGR2) encodes the non-ligand-binding beta chain of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. Defects in IFNGR2 are a cause of mendelian susceptibility to mycobacterial disease (MSMD), also known as familial disseminated atypical mycobacterial infection. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. [provided by RefSeq, Jul 2008]

IFNGR2 links:

TMEM50B (HGNC:1280): (transmembrane protein 50B) Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMEM50B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 21-33432659-T-C is Benign according to our data. Variant chr21-33432659-T-C is described in ClinVar as [Benign]. Clinvar id is 1268638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
IFNGR2	NM_005534.4 linkuse as main transcript	c.722-55T>C	intron_variant		ENST00000290219.11
TMEM50B	XM_011529746.3 linkuse as main transcript	c.*2374A>G	3_prime_UTR_variant	10/10
IFNGR2	NM_001329128.2 linkuse as main transcript	c.779-55T>C	intron_variant
TMEM50B	NR_040016.2 linkuse as main transcript	n.2919A>G	non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR2	ENST00000290219.11 linkuse as main transcript	c.722-55T>C		intron_variant		1	NM_005534.4	P1

Frequencies

GnomAD3 genomes

AF:

0.773

AC:

117515

AN:

152032

Hom.:

45937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.865

Gnomad AMI

AF:

0.636

Gnomad AMR

AF:

0.813

Gnomad ASJ

AF:

0.644

Gnomad EAS

AF:

0.984

Gnomad SAS

AF:

0.776

Gnomad FIN

AF:

0.794

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.743

GnomAD4 exome

AF:

0.725

AC:

1034793

AN:

1426972

Hom.:

378207

Cov.:

AF XY:

0.724

AC XY:

515612

AN XY:

712186

show subpopulations

Gnomad4 AFR exome

AF:

0.870

Gnomad4 AMR exome

AF:

0.852

Gnomad4 ASJ exome

AF:

0.645

Gnomad4 EAS exome

AF:

0.976

Gnomad4 SAS exome

AF:

0.765

Gnomad4 FIN exome

AF:

0.788

Gnomad4 NFE exome

AF:

0.702

Gnomad4 OTH exome

AF:

0.736

GnomAD4 genome

AF:

0.773

AC:

117631

AN:

152150

Hom.:

45996

Cov.:

AF XY:

0.780

AC XY:

58008

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.866

Gnomad4 AMR

AF:

0.814

Gnomad4 ASJ

AF:

0.644

Gnomad4 EAS

AF:

0.984

Gnomad4 SAS

AF:

0.776

Gnomad4 FIN

AF:

0.794

Gnomad4 NFE

AF:

0.698

Gnomad4 OTH

AF:

0.744

Alfa

AF:

0.720

Hom.:

17672

Bravo

AF:

0.781

Asia WGS

AF:

0.890

AC:

3096

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.37

DANN

Benign

0.36

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