Genetic Variant IFNGR1:c.85+570C>A (chr6-137218673-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000367739.9(IFNGR1):c.85+570C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000702 in 142,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IFNGR1
ENST00000367739.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.533

Publications

14 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

IFNGR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367739.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IFNGR1	NM_000416.3	MANE Select	c.85+570C>A	intron	N/A	NP_000407.1
IFNGR1	NM_001363527.1		c.-40C>A	splice_region	Exon 1 of 7	NP_001350456.1
IFNGR1	NM_001363527.1		c.-40C>A	5_prime_UTR	Exon 1 of 7	NP_001350456.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IFNGR1	ENST00000367739.9	TSL:1 MANE Select	c.85+570C>A	intron	N/A	ENSP00000356713.5
IFNGR1	ENST00000646898.1		c.-58C>A	splice_region	Exon 1 of 8	ENSP00000494069.1
IFNGR1	ENST00000644894.1		c.-40C>A	splice_region	Exon 1 of 7	ENSP00000495272.1

Frequencies

GnomAD3 genomes

AF:

0.00000702

AC:

AN:

142456

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

208154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

114206

African (AFR)

AF:

0.00

AC:

AN:

5496

American (AMR)

AF:

0.00

AC:

AN:

12886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4816

East Asian (EAS)

AF:

0.00

AC:

AN:

8278

South Asian (SAS)

AF:

0.00

AC:

AN:

44412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8984

Middle Eastern (MID)

AF:

0.00

AC:

AN:

712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

112678

Other (OTH)

AF:

0.00

AC:

AN:

9892

GnomAD4 genome

AF:

0.00000702

AC:

AN:

142456

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68164

show subpopulations

African (AFR)

AF:

0.0000261

AC:

AN:

38260

American (AMR)

AF:

0.00

AC:

AN:

12718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

4790

South Asian (SAS)

AF:

0.00

AC:

AN:

4622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67024

Other (OTH)

AF:

0.00

AC:

AN:

1970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

2600

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.0

(source)

DANN

Benign

0.78

PhyloP100

-0.53

PromoterAI

-0.093

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over