rs17181457

chr6-137219399-G-Achr6-137219399-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000414770.6(IFNGR1):c.-213C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 1,554,488 control chromosomes in the GnomAD database, including 4,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (279 hom., cov: 33)
  • Exomes 𝑓: 0.070 (3847 hom.)
• Consequence: IFNGR1 ENST00000414770.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.49

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=-0.81).
• BP6: Variant 6-137219399-G-A is Benign according to our data. Variant chr6-137219399-G-A is described in ClinVar as [Benign]. Clinvar id is 355566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR1	NM_000416.3			upstream_gene_variant		ENST00000367739.9
IFNGR1	XM_011535793.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR1	ENST00000367739.9			upstream_gene_variant		1	NM_000416.3	P2

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7910 AN: 152194 Hom.: 280 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0697 AC: 97793 AN: 1402178 Hom.: 3847 Cov.: 33 AF XY: 0.0690 AC XY: 47710 AN XY: 691944

Gnomad4 AFR exome AF: 0.0109

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.000634

Gnomad4 SAS exome AF: 0.0472

Gnomad4 FIN exome AF: 0.0709

Gnomad4 NFE exome AF: 0.0754

Gnomad4 OTH exome AF: 0.0652

GnomAD4 genome AF: 0.0519 AC: 7907 AN: 152310 Hom.: 279 Cov.: 33 AF XY: 0.0512 AC XY: 3810 AN XY: 74484

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0534

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0449

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0738

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0247 Hom.: 11

Bravo AF: 0.0484

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency 27A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.21
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17181457; hg19: chr6-137540536;