rs3799488

Positions:

chr6-137198643-T-C

Variant summary

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

The NM_000416.3(IFNGR1):c.862-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,605,704 control chromosomes in the GnomAD database, including 12,087 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 919 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11168 hom. )

Consequence

IFNGR1
NM_000416.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003753

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.00900

Variant links:

Genes affected

IFNGR1 (HGNC:5439): (interferon gamma receptor 1) This gene (IFNGR1) encodes the ligand-binding chain (alpha) of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. A genetic variation in IFNGR1 is associated with susceptibility to Helicobacter pylori infection. In addition, defects in IFNGR1 are a cause of mendelian susceptibility to mycobacterial disease, also known as familial disseminated atypical mycobacterial infection. [provided by RefSeq, Jul 2008]

IFNGR1 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=-0.81).

BP6

Variant 6-137198643-T-C is Benign according to our data. Variant chr6-137198643-T-C is described in ClinVar as [Benign]. Clinvar id is 355555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137198643-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR1	NM_000416.3 linkuse as main transcript	c.862-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR1	ENST00000367739.9 linkuse as main transcript	c.862-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000416.3	P2	P15260-1

Frequencies

GnomAD3 genomes

AF:

0.0945

AC:

14349

AN:

151898

Hom.:

915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0207

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0994

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0845

GnomAD3 exomes

AF:

0.119

AC:

29206

AN:

245934

Hom.:

2035

AF XY:

0.119

AC XY:

15952

AN XY:

133630

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.0981

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.118

AC:

171430

AN:

1453688

Hom.:

11168

Cov.:

AF XY:

0.117

AC XY:

84901

AN XY:

723620

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.283

Gnomad4 SAS exome

AF:

0.0986

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.0945

AC:

14361

AN:

152016

Hom.:

919

Cov.:

AF XY:

0.0949

AC XY:

7053

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0206

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.259

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.0994

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.0831

Alfa

AF:

0.114

Hom.:

1765

Bravo

AF:

0.0919

Asia WGS

AF:

0.145

AC:

505

AN:

3478

EpiCase

AF:

0.111

EpiControl

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Disseminated atypical mycobacterial infection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Immunodeficiency 27A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0

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