rs9376267

chr6-137209894-C-T

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/exons	MANE	UniProt
IFNGR1	NM_000416.3	c.86-2817G>A		intron_variant		ENST00000367739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR1	ENST00000367739.9	c.86-2817G>A		intron_variant		1	NM_000416.3	P2

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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;