rs11914

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

37 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
immunodeficiency 27A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFNGR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
IFNGR1	NM_000416.3 link	c.1050T>G	p.Ser350Ser	synonymous_variant	Exon 7 of 7	ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9 link	c.1050T>G	p.Ser350Ser	synonymous_variant	Exon 7 of 7	1	NM_000416.3	ENSP00000356713.5

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

GnomAD2 exomes

AF:

0.132

AC:

33088

AN:

251366

AF XY:

0.134

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 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

African (AFR)

AF:

0.0626

AC:

2097

AN:

33480

American (AMR)

AF:

0.0886

AC:

3961

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

5586

AN:

26136

East Asian (EAS)

AF:

0.0856

AC:

3397

AN:

39700

South Asian (SAS)

AF:

0.0868

AC:

7490

AN:

86258

European-Finnish (FIN)

AF:

0.113

AC:

6022

AN:

53412

Middle Eastern (MID)

AF:

0.187

AC:

1076

AN:

5768

European-Non Finnish (NFE)

AF:

0.162

AC:

179742

AN:

1112004

Other (OTH)

AF:

0.151

AC:

9124

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

11663

23326

34988

46651

58314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6210

12420

18630

24840

31050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.125

AC:

18983

AN:

152180

Hom.:

1340

Cov.:

AF XY:

0.121

AC XY:

9024

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0653

AC:

2711

AN:

41526

American (AMR)

AF:

0.110

AC:

1678

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

739

AN:

3472

East Asian (EAS)

AF:

0.119

AC:

619

AN:

5186

South Asian (SAS)

AF:

0.0898

AC:

433

AN:

4822

European-Finnish (FIN)

AF:

0.104

AC:

1099

AN:

10596

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11143

AN:

68002

Other (OTH)

AF:

0.148

AC:

313

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

845

1689

2534

3378

4223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.149

Hom.:

1717

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

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. -

Disseminated atypical mycobacterial infection

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency 27A

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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

(source)

DANN

Benign

0.44

PhyloP100

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over