6-137198101-A-G

Position:

chr6-137198101-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000416.3(IFNGR1):c.1400T>C(p.Leu467Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,614,140 control chromosomes in the GnomAD database, including 3,621 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 244 hom., cov: 32)

Exomes 𝑓: 0.021 ( 3377 hom. )

Consequence

IFNGR1
NM_000416.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.394

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009924144).

BP6

Variant 6-137198101-A-G is Benign according to our data. Variant chr6-137198101-A-G is described in ClinVar as [Benign]. Clinvar id is 355552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-137198101-A-G is described in Lovd as [Likely_benign]. Variant chr6-137198101-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR1	NM_000416.3 linkuse as main transcript	c.1400T>C	p.Leu467Pro	missense_variant	7/7	ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9 linkuse as main transcript	c.1400T>C	p.Leu467Pro	missense_variant	7/7	1	NM_000416.3	ENSP00000356713	P2	P15260-1

Frequencies

GnomAD3 genomes

AF:

0.0207

AC:

3143

AN:

152166

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.0443

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.0229

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0512

AC:

12858

AN:

251306

Hom.:

1328

AF XY:

0.0593

AC XY:

8052

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.0846

Gnomad ASJ exome

AF:

0.00665

Gnomad EAS exome

AF:

0.0466

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.0296

GnomAD4 exome

AF:

0.0214

AC:

31215

AN:

1461856

Hom.:

3377

Cov.:

AF XY:

0.0280

AC XY:

20347

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.0787

Gnomad4 ASJ exome

AF:

0.00559

Gnomad4 EAS exome

AF:

0.0353

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.0198

Gnomad4 NFE exome

AF:

0.000762

Gnomad4 OTH exome

AF:

0.0285

GnomAD4 genome

AF:

0.0208

AC:

3167

AN:

152284

Hom.:

244

Cov.:

AF XY:

0.0263

AC XY:

1961

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.0378

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.0448

Gnomad4 SAS

AF:

0.278

Gnomad4 FIN

AF:

0.0229

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.0299

Alfa

AF:

0.00689

Hom.:

139

Bravo

AF:

0.0160

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.0518

AC:

6288

Asia WGS

AF:

0.215

AC:

745

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Disseminated atypical mycobacterial infection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Immunodeficiency 27A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

5.8

DANN

Benign

0.93

DEOGEN2

Benign

0.34

T;.;.;.;.;.;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.52

T;.;T;.;.;T;T

MetaRNN

Benign

0.0099

T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;.;.;.;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.3

D;.;.;.;.;.;.

REVEL

Benign

0.11

Sift

Benign

0.12

T;.;.;.;.;.;.

Sift4G

Benign

0.10

T;.;.;.;.;.;.

Polyphen

0.26

B;.;.;.;.;.;.

Vest4

0.10

MPC

0.11

ClinPred

0.021

GERP RS

2.0

Varity_R

0.65

gMVP

0.52

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.

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