rs1327475

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000416.3(IFNGR1):​c.85+3925C>T variant causes a intron 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. 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_000416.3 intron

Scores

1
1
12

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.447
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IFNGR1NM_000416.3 linkuse as main transcriptc.85+3925C>T intron_variant ENST00000367739.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IFNGR1ENST00000367739.9 linkuse as main transcriptc.85+3925C>T intron_variant 1 NM_000416.3 P2P15260-1

Frequencies

GnomAD3 genomes
AF:
0.122
AC:
18582
AN:
152046
Hom.:
1294
Cov.:
32
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
GnomAD3 exomes
AF:
0.128
AC:
18943
AN:
147932
Hom.:
1391
AF XY:
0.128
AC XY:
10206
AN XY:
79680
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 SAS exome
AF:
0.0839
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.:
31
AF XY:
0.148
AC XY:
101391
AN XY:
687266
show subpopulations
Gnomad4 AFR exome
AF:
0.0555
Gnomad4 AMR exome
AF:
0.0896
Gnomad4 ASJ exome
AF:
0.212
Gnomad4 EAS exome
AF:
0.0822
Gnomad4 SAS exome
AF:
0.0848
Gnomad4 FIN exome
AF:
0.112
Gnomad4 NFE exome
AF:
0.160
Gnomad4 OTH exome
AF:
0.149
GnomAD4 genome
AF:
0.122
AC:
18581
AN:
152164
Hom.:
1297
Cov.:
32
AF XY:
0.119
AC XY:
8842
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0581
Gnomad4 AMR
AF:
0.109
Gnomad4 ASJ
AF:
0.212
Gnomad4 EAS
AF:
0.120
Gnomad4 SAS
AF:
0.0891
Gnomad4 FIN
AF:
0.104
Gnomad4 NFE
AF:
0.163
Gnomad4 OTH
AF:
0.148
Alfa
AF:
0.147
Hom.:
912
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

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

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
6.1
DANN
Uncertain
1.0
DEOGEN2
Benign
0.028
.;.;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.073
N
LIST_S2
Benign
0.27
.;T;T
MetaRNN
Benign
0.0016
T;T;T
MetaSVM
Benign
-0.76
T
MutationTaster
Benign
1.0
P;P
PROVEAN
Benign
-0.52
.;.;N
REVEL
Benign
0.090
Sift
Pathogenic
0.0
.;.;D
ClinPred
0.011
T
GERP RS
1.4

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1327475; hg19: chr6-137536455; COSMIC: COSV62990076; API