6-137219286-C-T

Position:

chr6-137219286-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000416.3(IFNGR1):c.42G>A(p.Val14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00966 in 1,611,826 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 3 hom., cov: 33)

Exomes 𝑓: 0.010 ( 111 hom. )

Consequence

IFNGR1
NM_000416.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.669

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 6-137219286-C-T is Benign according to our data. Variant chr6-137219286-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 36374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.669 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0061 (930/152356) while in subpopulation NFE AF= 0.0105 (715/68028). AF 95% confidence interval is 0.00987. There are 3 homozygotes in gnomad4. There are 433 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR1	NM_000416.3 linkuse as main transcript	c.42G>A	p.Val14=	synonymous_variant	1/7	ENST00000367739.9	NP_000407.1
IFNGR1	XM_011535793.3 linkuse as main transcript	c.-100G>A		5_prime_UTR_variant	1/8		XP_011534095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9 linkuse as main transcript	c.42G>A	p.Val14=	synonymous_variant	1/7	1	NM_000416.3	ENSP00000356713	P2	P15260-1

Frequencies

GnomAD3 genomes

AF:

0.00611

AC:

930

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00593

AC:

1446

AN:

243840

Hom.:

AF XY:

0.00587

AC XY:

776

AN XY:

132188

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.00284

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.00168

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00623

GnomAD4 exome

AF:

0.0100

AC:

14634

AN:

1459470

Hom.:

111

Cov.:

AF XY:

0.00982

AC XY:

7129

AN XY:

725788

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00416

Gnomad4 ASJ exome

AF:

0.00304

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.00226

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00774

GnomAD4 genome

AF:

0.00610

AC:

930

AN:

152356

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

433

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00966

Hom.:

Bravo

AF:

0.00659

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	IFNGR1: BP4, BP7, BS1, BS2 -

Disseminated atypical mycobacterial infection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Interferon gamma receptor deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing;curation

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 18, 2011

- -

IFNGR1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Immunodeficiency 27A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

-0.69

CADD

Benign

6.9

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over