6-137219233-A-G

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.85+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,602,902 control chromosomes in the GnomAD database, including 138,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14807 hom., cov: 32)

Exomes 𝑓: 0.41 ( 123435 hom. )

Consequence

IFNGR1
NM_000416.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.0250

Publications

46 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=-0.85).

BP6

Variant 6-137219233-A-G is Benign according to our data. Variant chr6-137219233-A-G is described in ClinVar as Benign. ClinVar VariationId is 355562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.61 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.85+10T>C	intron	N/A	NP_000407.1	A0A0S2Z3Y2
IFNGR1	NM_001363526.1		c.-306T>C	upstream_gene	N/A	NP_001350455.1	A0A2R8Y4U4
IFNGR1	NM_001363527.1		c.-600T>C	upstream_gene	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.85+10T>C	intron	N/A	ENSP00000356713.5	P15260-1
IFNGR1	ENST00000644894.1		c.-600T>C	5_prime_UTR	Exon 1 of 7	ENSP00000495272.1	A0A2R8YFL3
IFNGR1	ENST00000957752.1		c.85+10T>C	intron	N/A	ENSP00000627811.1

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

66181

AN:

151938

Hom.:

14762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.469

GnomAD2 exomes

AF:

0.431

AC:

98680

AN:

229126

AF XY:

0.440

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

AF:

0.407

AC:

590179

AN:

1450846

Hom.:

123435

Cov.:

AF XY:

0.413

AC XY:

297737

AN XY:

720686

show subpopulations

African (AFR)

AF:

0.516

AC:

17211

AN:

33372

American (AMR)

AF:

0.359

AC:

15441

AN:

43058

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

12821

AN:

25756

East Asian (EAS)

AF:

0.541

AC:

21246

AN:

39256

South Asian (SAS)

AF:

0.605

AC:

51011

AN:

84368

European-Finnish (FIN)

AF:

0.365

AC:

19082

AN:

52296

Middle Eastern (MID)

AF:

0.495

AC:

2722

AN:

5496

European-Non Finnish (NFE)

AF:

0.383

AC:

424508

AN:

1107324

Other (OTH)

AF:

0.436

AC:

26137

AN:

59920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

18491

36982

55472

73963

92454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13516

27032

40548

54064

67580

<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:

0.436

AC:

66286

AN:

152056

Hom.:

14807

Cov.:

AF XY:

0.439

AC XY:

32657

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.506

AC:

20980

AN:

41464

American (AMR)

AF:

0.394

AC:

6025

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1752

AN:

3468

East Asian (EAS)

AF:

0.577

AC:

2972

AN:

5148

South Asian (SAS)

AF:

0.628

AC:

3034

AN:

4830

European-Finnish (FIN)

AF:

0.354

AC:

3744

AN:

10586

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.386

AC:

26260

AN:

67968

Other (OTH)

AF:

0.471

AC:

991

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1933

3866

5798

7731

9664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.403

Hom.:

14759

Bravo

AF:

0.435

Asia WGS

AF:

0.631

AC:

2191

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 27A (2)

not specified (2)

Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (1)

Disseminated atypical mycobacterial infection (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.5

(source)

DANN

Benign

0.66

PhyloP100

0.025

PromoterAI

-0.061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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