rs1327475

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/16 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

Publications

30 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363526.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IFNGR1	NM_000416.3	MANE Select	c.85+3925C>T		intron	N/A	NP_000407.1
IFNGR1	NM_001363526.1		c.4C>T	p.Leu2Phe	missense	Exon 2 of 8	NP_001350455.1
IFNGR1	NM_001363527.1		c.-39+3354C>T		intron	N/A	NP_001350456.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IFNGR1	ENST00000367739.9	TSL:1 MANE Select	c.85+3925C>T		intron	N/A	ENSP00000356713.5
IFNGR1	ENST00000414770.6	TSL:3	c.4C>T	p.Leu2Phe	missense	Exon 2 of 8	ENSP00000394230.2
IFNGR1	ENST00000646036.1		c.4C>T	p.Leu2Phe	missense	Exon 2 of 8	ENSP00000496387.1

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

GnomAD2 exomes

AF:

0.128

AC:

18943

AN:

147932

AF XY:

0.128

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 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

African (AFR)

AF:

0.0555

AC:

1749

AN:

31514

American (AMR)

AF:

0.0896

AC:

3174

AN:

35432

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

5310

AN:

25050

East Asian (EAS)

AF:

0.0822

AC:

2925

AN:

35586

South Asian (SAS)

AF:

0.0848

AC:

6679

AN:

78798

European-Finnish (FIN)

AF:

0.112

AC:

5377

AN:

48058

Middle Eastern (MID)

AF:

0.184

AC:

1040

AN:

5662

European-Non Finnish (NFE)

AF:

0.160

AC:

172080

AN:

1075584

Other (OTH)

AF:

0.149

AC:

8605

AN:

57766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

8521

17042

25564

34085

42606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6060

12120

18180

24240

30300

<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:

0.122

AC:

18581

AN:

152164

Hom.:

1297

Cov.:

AF XY:

0.119

AC XY:

8842

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0581

AC:

2413

AN:

41524

American (AMR)

AF:

0.109

AC:

1668

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

733

AN:

3464

East Asian (EAS)

AF:

0.120

AC:

620

AN:

5184

South Asian (SAS)

AF:

0.0891

AC:

429

AN:

4814

European-Finnish (FIN)

AF:

0.104

AC:

1104

AN:

10584

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11053

AN:

67980

Other (OTH)

AF:

0.148

AC:

313

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

846

1691

2537

3382

4228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.136

Hom.:

1201

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

6.1

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.76

PhyloP100

0.45

PROVEAN

Benign

-0.52

REVEL

Benign

0.090

Sift

Pathogenic

0.0

ClinPred

0.011

GERP RS

1.4

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over