rs3799488

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000416.3(IFNGR1):c.862-4A>G variant causes a splice region, 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, intron

Scores

Splicing: ADA: 0.00003753

Clinical Significance

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

Conservation

PhyloP100: 0.00900

Publications

47 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
immunodeficiency 27A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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 -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 VariationId is 355555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFNGR1	NM_000416.3	MANE Select	c.862-4A>G	splice_region intron	N/A	NP_000407.1	A0A0S2Z3Y2
IFNGR1	NM_001363526.1		c.832-4A>G	splice_region intron	N/A	NP_001350455.1	A0A2R8Y4U4
IFNGR1	NM_001363527.1		c.739-4A>G	splice_region intron	N/A	NP_001350456.1	A0A2R8YFL3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFNGR1	ENST00000367739.9	TSL:1 MANE Select	c.862-4A>G	splice_region intron	N/A	ENSP00000356713.5	P15260-1
IFNGR1	ENST00000957752.1		c.856-4A>G	splice_region intron	N/A	ENSP00000627811.1
IFNGR1	ENST00000414770.6	TSL:3	c.832-4A>G	splice_region intron	N/A	ENSP00000394230.2	A0A2R8Y4U4

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

GnomAD2 exomes

AF:

0.119

AC:

29206

AN:

245934

AF XY:

0.119

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 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

African (AFR)

AF:

0.0176

AC:

589

AN:

33400

American (AMR)

AF:

0.111

AC:

4957

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3912

AN:

26102

East Asian (EAS)

AF:

0.283

AC:

11216

AN:

39672

South Asian (SAS)

AF:

0.0986

AC:

8485

AN:

86088

European-Finnish (FIN)

AF:

0.110

AC:

5458

AN:

49686

Middle Eastern (MID)

AF:

0.0865

AC:

436

AN:

5040

European-Non Finnish (NFE)

AF:

0.117

AC:

129408

AN:

1108946

Other (OTH)

AF:

0.116

AC:

6969

AN:

60128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

6664

13329

19993

26658

33322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4714

9428

14142

18856

23570

<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:

0.0945

AC:

14361

AN:

152016

Hom.:

919

Cov.:

AF XY:

0.0949

AC XY:

7053

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0206

AC:

855

AN:

41488

American (AMR)

AF:

0.122

AC:

1870

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

514

AN:

3470

East Asian (EAS)

AF:

0.259

AC:

1334

AN:

5154

South Asian (SAS)

AF:

0.100

AC:

482

AN:

4800

European-Finnish (FIN)

AF:

0.0994

AC:

1050

AN:

10562

Middle Eastern (MID)

AF:

0.0651

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.117

AC:

7964

AN:

67964

Other (OTH)

AF:

0.0831

AC:

175

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

637

1273

1910

2546

3183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.112

Hom.:

2484

Bravo

AF:

0.0919

Asia WGS

AF:

0.145

AC:

505

AN:

3478

EpiCase

AF:

0.111

EpiControl

AF:

0.112

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Disseminated atypical mycobacterial infection (1)

Immunodeficiency 27A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

(source)

DANN

Benign

0.61

PhyloP100

0.0090

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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