Variant chr6-137198451-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000416.3(IFNGR1):c.1050T>G(p.Ser350Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,614,050 control chromosomes in the GnomAD database, including 18,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1340 hom., cov: 31)

Exomes 𝑓: 0.15 ( 17198 hom. )

Consequence

IFNGR1
NM_000416.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.671

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-137198451-A-C is Benign according to our data. Variant chr6-137198451-A-C is described in ClinVar as [Benign]. Clinvar id is 355554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.671 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR1	NM_000416.3 linkuse as main transcript	c.1050T>G	p.Ser350Ser	synonymous_variant	7/7	ENST00000367739.9	NP_000407.1	P15260-1A0A0S2Z3Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9 linkuse as main transcript	c.1050T>G	p.Ser350Ser	synonymous_variant	7/7	1	NM_000416.3	ENSP00000356713.5		P15260-1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18983

AN:

152062

Hom.:

1336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0903

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.132

AC:

33088

AN:

251366

Hom.:

2476

AF XY:

0.134

AC XY:

18188

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0632

Gnomad AMR exome

AF:

0.0850

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.0859

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.149

AC:

218495

AN:

1461870

Hom.:

17198

Cov.:

AF XY:

0.149

AC XY:

108160

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0626

Gnomad4 AMR exome

AF:

0.0886

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.0856

Gnomad4 SAS exome

AF:

0.0868

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.125

AC:

18983

AN:

152180

Hom.:

1340

Cov.:

AF XY:

0.121

AC XY:

9024

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0653

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0898

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.149

Hom.:

1327

Bravo

AF:

0.124

Asia WGS

AF:

0.104

AC:

363

AN:

3478

EpiCase

AF:

0.184

EpiControl

AF:

0.189

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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: MAF -
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 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Disseminated atypical mycobacterial infection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 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. -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.41

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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