rs9376267

Variant names:

• chr6-137209894-C-T
• rs9376267
• NM_000416.3:c.86-2817G>A

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.86-2817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 398,504 control chromosomes in the GnomAD database, including 13,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4593 hom., cov: 32)
  • Exomes 𝑓: 0.26 (9005 hom.)
• Consequence: IFNGR1 NM_000416.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.151

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=-0.89).
• BP6: Variant 6-137209894-C-T is Benign according to our data. Variant chr6-137209894-C-T is described in ClinVar as [Benign]. Clinvar id is 2688425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.86-2817G>A		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.86-2817G>A		intron_variant	Intron 1 of 6	1	NM_000416.3	ENSP00000356713.5

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35035 AN: 152054 Hom.: 4576 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.260 AC: 64120 AN: 246332 Hom.: 9005 Cov.: 0 AF XY: 0.261 AC XY: 32547 AN XY: 124834

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.254

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.540

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.231 AC: 35092 AN: 152172 Hom.: 4593 Cov.: 32 AF XY: 0.238 AC XY: 17720 AN XY: 74384

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.244

Alfa AF: 0.240 Hom.: 8042

Bravo AF: 0.220

Asia WGS AF: 0.490 AC: 1699 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 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 40. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9376267; hg19: chr6-137531031;