Genetic Variant NM_000416.3: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 NM_000416.3(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
NM_000416.3 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: NM_000416.3. 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

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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