chr6-137210055-T-C

Variant names:

• chr6-137210055-T-C
• rs9402879
• NM_000416.3:c.86-2978A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000416.3(IFNGR1):​c.86-2978A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 390,704 control chromosomes in the GnomAD database, including 11,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3476 hom., cov: 32)
  • Exomes 𝑓: 0.24 (7658 hom.)
• Consequence: IFNGR1 NM_000416.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0910
• Publications: 2 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: 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-137210055-T-C is Benign according to our data. Variant chr6-137210055-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.86-2978A>G		intron_variant	Intron 1 of 6	ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9	c.86-2978A>G		intron_variant	Intron 1 of 6	1	NM_000416.3	ENSP00000356713.5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30474 AN: 152038 Hom.: 3469 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.245 AC: 58437 AN: 238548 Hom.: 7658 AF XY: 0.246 AC XY: 29738 AN XY: 120960

African (AFR) AF: 0.103 AC: 720 AN: 7006

American (AMR) AF: 0.193 AC: 1388 AN: 7180

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 2381 AN: 9020

East Asian (EAS) AF: 0.420 AC: 9403 AN: 22410

South Asian (SAS) AF: 0.243 AC: 537 AN: 2208

European-Finnish (FIN) AF: 0.217 AC: 4325 AN: 19960

Middle Eastern (MID) AF: 0.229 AC: 290 AN: 1268

European-Non Finnish (NFE) AF: 0.232 AC: 35676 AN: 153580

Other (OTH) AF: 0.234 AC: 3717 AN: 15916

GnomAD4 genome AF: 0.201 AC: 30510 AN: 152156 Hom.: 3476 Cov.: 32 AF XY: 0.203 AC XY: 15099 AN XY: 74390

African (AFR) AF: 0.0982 AC: 4078 AN: 41528

American (AMR) AF: 0.215 AC: 3285 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2067 AN: 5174

South Asian (SAS) AF: 0.264 AC: 1274 AN: 4824

European-Finnish (FIN) AF: 0.212 AC: 2238 AN: 10576

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15944 AN: 67984

Other (OTH) AF: 0.206 AC: 435 AN: 2112

Alfa AF: 0.202 Hom.: 456

Bravo AF: 0.193

Asia WGS AF: 0.279 AC: 967 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.54
PhyloP100		-0.091
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: rs9402879; hg19: chr6-137531192; COSMIC: COSV62990272;