Variant chr6-137215318-G-A 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_001363526.1(IFNGR1):c.4C>T(p.Leu2Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,545,614 control chromosomes in the GnomAD database, including 17,597 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1297 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16300 hom. )

Consequence

IFNGR1
NM_001363526.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.447

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015720427).

BP6

Variant 6-137215318-G-A is Benign according to our data. Variant chr6-137215318-G-A is described in ClinVar as [Benign]. Clinvar id is 2688498.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR1	NM_000416.3 link	c.85+3925C>T		intron_variant	Intron 1 of 6	ENST00000367739.9	NP_000407.1	P15260-1A0A0S2Z3Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9 link	c.85+3925C>T		intron_variant	Intron 1 of 6	1	NM_000416.3	ENSP00000356713.5		P15260-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18582

AN:

152046

Hom.:

1294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0581

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0897

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.128

AC:

18943

AN:

147932

Hom.:

1391

AF XY:

0.128

AC XY:

10206

AN XY:

79680

show subpopulations

Gnomad AFR exome

AF:

0.0535

Gnomad AMR exome

AF:

0.0863

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.0839

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.149

AC:

206939

AN:

1393450

Hom.:

16300

Cov.:

AF XY:

0.148

AC XY:

101391

AN XY:

687266

show subpopulations

Gnomad4 AFR exome

AF:

0.0555

Gnomad4 AMR exome

AF:

0.0896

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.0822

Gnomad4 SAS exome

AF:

0.0848

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.149

GnomAD4 genome

AF:

0.122

AC:

18581

AN:

152164

Hom.:

1297

Cov.:

AF XY:

0.119

AC XY:

8842

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0581

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.0891

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.163

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.147

Hom.:

912

Bravo

AF:

0.121

TwinsUK

AF:

0.155

AC:

575

ALSPAC

AF:

0.155

AC:

598

ExAC

AF:

0.113

AC:

2065

Asia WGS

AF:

0.104

AC:

360

AN:

3444

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

6.1

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

.;.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.27

.;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-0.76

PROVEAN

Benign

-0.52

.;.;N

REVEL

Benign

0.090

Sift

Pathogenic

0.0

.;.;D

ClinPred

0.011

GERP RS

1.4

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