6-137210055-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.234

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

Gnomad4 AFR AF: 0.0982

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.206

Alfa AF: 0.207 Hom.: 453

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

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

Other links and lift over

dbSNP: rs9402879; hg19: chr6-137531192; COSMIC: COSV62990272;