6-137197903-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000416.3(IFNGR1):​c.*128G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,239,116 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

IFNGR1
NM_000416.3 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.351
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 (BayesDel_noAF=-0.89).
BP6
Variant 6-137197903-C-A is Benign according to our data. Variant chr6-137197903-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 355550.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.002 (304/151706) while in subpopulation AFR AF= 0.00684 (283/41366). AF 95% confidence interval is 0.00619. There are 2 homozygotes in gnomad4. There are 153 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IFNGR1NM_000416.3 linkuse as main transcriptc.*128G>T 3_prime_UTR_variant 7/7 ENST00000367739.9 NP_000407.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IFNGR1ENST00000367739.9 linkuse as main transcriptc.*128G>T 3_prime_UTR_variant 7/71 NM_000416.3 ENSP00000356713 P2P15260-1

Frequencies

GnomAD3 genomes
AF:
0.00202
AC:
306
AN:
151634
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00688
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000854
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00321
Gnomad NFE
AF:
0.0000589
Gnomad OTH
AF:
0.00192
GnomAD4 exome
AF:
0.000205
AC:
223
AN:
1087410
Hom.:
0
Cov.:
14
AF XY:
0.000157
AC XY:
87
AN XY:
554898
show subpopulations
Gnomad4 AFR exome
AF:
0.00575
Gnomad4 AMR exome
AF:
0.000719
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000396
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000634
Gnomad4 OTH exome
AF:
0.000670
GnomAD4 genome
AF:
0.00200
AC:
304
AN:
151706
Hom.:
2
Cov.:
32
AF XY:
0.00207
AC XY:
153
AN XY:
74090
show subpopulations
Gnomad4 AFR
AF:
0.00684
Gnomad4 AMR
AF:
0.000853
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00176
Hom.:
0
Bravo
AF:
0.00184
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

Immunodeficiency 27A Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.50
DANN
Benign
0.46

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: rs7769141; hg19: chr6-137519040; API