chr6-137218368-C-G

Variant names:

• chr6-137218368-C-G
• rs9376269
• NM_000416.3:c.85+875G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000416.3(IFNGR1):​c.85+875G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 640,188 control chromosomes in the GnomAD database, including 26,551 homozygotes. 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 0.23 (4529 hom., cov: 32)
  • Exomes 𝑓: 0.28 (22022 hom.)
• Consequence: IFNGR1 NM_000416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585
• Publications: 7 publications found

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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• immunodeficiency 27A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR1	NM_000416.3	MANE Select	c.85+875G>C		intron	N/A	NP_000407.1	A0A0S2Z3Y2
	IFNGR1	NM_001363526.1		c.-57+616G>C		intron	N/A	NP_001350455.1	A0A2R8Y4U4
	IFNGR1	NM_001363527.1		c.-39+304G>C		intron	N/A	NP_001350456.1	A0A2R8YFL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR1	ENST00000367739.9	TSL:1 MANE Select	c.85+875G>C		intron	N/A	ENSP00000356713.5	P15260-1
	IFNGR1	ENST00000957752.1		c.85+875G>C		intron	N/A	ENSP00000627811.1
	IFNGR1	ENST00000414770.6	TSL:3	c.-57+875G>C		intron	N/A	ENSP00000394230.2	A0A2R8Y4U4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34671 AN: 151914 Hom.: 4509 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.280 AC: 136738 AN: 488154 Hom.: 22022 AF XY: 0.298 AC XY: 77550 AN XY: 260552

African (AFR) AF: 0.135 AC: 1631 AN: 12064

American (AMR) AF: 0.256 AC: 7032 AN: 27490

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 3288 AN: 12048

East Asian (EAS) AF: 0.462 AC: 4628 AN: 10028

South Asian (SAS) AF: 0.522 AC: 33155 AN: 63522

European-Finnish (FIN) AF: 0.244 AC: 3028 AN: 12402

Middle Eastern (MID) AF: 0.241 AC: 758 AN: 3142

European-Non Finnish (NFE) AF: 0.237 AC: 77660 AN: 327242

Other (OTH) AF: 0.275 AC: 5558 AN: 20216

GnomAD4 genome AF: 0.228 AC: 34732 AN: 152034 Hom.: 4529 Cov.: 32 AF XY: 0.236 AC XY: 17533 AN XY: 74314

African (AFR) AF: 0.140 AC: 5813 AN: 41478

American (AMR) AF: 0.254 AC: 3876 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.453 AC: 2342 AN: 5168

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4822

European-Finnish (FIN) AF: 0.234 AC: 2470 AN: 10550

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15960 AN: 67960

Other (OTH) AF: 0.238 AC: 502 AN: 2110

Alfa AF: 0.225 Hom.: 476

Bravo AF: 0.218

Asia WGS AF: 0.495 AC: 1716 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.52
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9376269; hg19: chr6-137539505;