rs17181457

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000414770.6(IFNGR1):​c.-213C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 1,554,488 control chromosomes in the GnomAD database, including 4,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.052 ( 279 hom., cov: 33)
Exomes 𝑓: 0.070 ( 3847 hom. )

Consequence

IFNGR1
ENST00000414770.6 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.49

Publications

8 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

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 (BayesDel_noAF=-0.81).
BP6
Variant 6-137219399-G-A is Benign according to our data. Variant chr6-137219399-G-A is described in ClinVar as Benign. ClinVar VariationId is 355566.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFNGR1NM_000416.3 linkc.-72C>T upstream_gene_variant ENST00000367739.9 NP_000407.1 P15260-1A0A0S2Z3Y2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFNGR1ENST00000367739.9 linkc.-72C>T upstream_gene_variant 1 NM_000416.3 ENSP00000356713.5 P15260-1

Frequencies

GnomAD3 genomes
AF:
0.0520
AC:
7910
AN:
152194
Hom.:
280
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0129
Gnomad AMI
AF:
0.0439
Gnomad AMR
AF:
0.0534
Gnomad ASJ
AF:
0.127
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.0451
Gnomad FIN
AF:
0.0670
Gnomad MID
AF:
0.0506
Gnomad NFE
AF:
0.0738
Gnomad OTH
AF:
0.0502
GnomAD4 exome
AF:
0.0697
AC:
97793
AN:
1402178
Hom.:
3847
Cov.:
33
AF XY:
0.0690
AC XY:
47710
AN XY:
691944
show subpopulations
African (AFR)
AF:
0.0109
AC:
348
AN:
32002
American (AMR)
AF:
0.0396
AC:
1417
AN:
35824
Ashkenazi Jewish (ASJ)
AF:
0.125
AC:
3145
AN:
25120
East Asian (EAS)
AF:
0.000634
AC:
23
AN:
36286
South Asian (SAS)
AF:
0.0472
AC:
3750
AN:
79486
European-Finnish (FIN)
AF:
0.0709
AC:
3476
AN:
49054
Middle Eastern (MID)
AF:
0.0672
AC:
371
AN:
5520
European-Non Finnish (NFE)
AF:
0.0754
AC:
81476
AN:
1080778
Other (OTH)
AF:
0.0652
AC:
3787
AN:
58108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
4536
9072
13609
18145
22681
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
3012
6024
9036
12048
15060
<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:
0.0519
AC:
7907
AN:
152310
Hom.:
279
Cov.:
33
AF XY:
0.0512
AC XY:
3810
AN XY:
74484
show subpopulations
African (AFR)
AF:
0.0129
AC:
536
AN:
41572
American (AMR)
AF:
0.0534
AC:
817
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.127
AC:
440
AN:
3468
East Asian (EAS)
AF:
0.00135
AC:
7
AN:
5184
South Asian (SAS)
AF:
0.0449
AC:
217
AN:
4830
European-Finnish (FIN)
AF:
0.0670
AC:
711
AN:
10614
Middle Eastern (MID)
AF:
0.0445
AC:
13
AN:
292
European-Non Finnish (NFE)
AF:
0.0738
AC:
5022
AN:
68020
Other (OTH)
AF:
0.0492
AC:
104
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
400
800
1200
1600
2000
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
94
188
282
376
470
<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:
0.0247
Hom.:
11
Bravo
AF:
0.0484
Asia WGS
AF:
0.0230
AC:
81
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Immunodeficiency 27A Benign:1
Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.21
DANN
Benign
0.75
PhyloP100
-2.5
PromoterAI
-0.15
Neutral
Mutation Taster
=300/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs17181457; hg19: chr6-137540536; API