6-137197825-T-C

Position:

• chr6-137197825-T-C

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.*206A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 566,144 control chromosomes in the GnomAD database, including 1,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (235 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1630 hom.)
• Consequence: IFNGR1 NM_000416.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00400

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=-0.9).
• BP6: Variant 6-137197825-T-C is Benign according to our data. Variant chr6-137197825-T-C is described in ClinVar as [Benign]. Clinvar id is 355549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.*206A>G		3_prime_UTR_variant	7/7	ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9	c.*206A>G		3_prime_UTR_variant	7/7	1	NM_000416.3	ENSP00000356713	P2

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2609 AN: 151620 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.00284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.0443

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.0226

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0216

GnomAD4 exome AF: 0.0335 AC: 13891 AN: 414408 Hom.: 1630 Cov.: 5 AF XY: 0.0458 AC XY: 10101 AN XY: 220400

Gnomad4 AFR exome AF: 0.00163

Gnomad4 AMR exome AF: 0.0577

Gnomad4 ASJ exome AF: 0.00453

Gnomad4 EAS exome AF: 0.0310

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.00110

Gnomad4 OTH exome AF: 0.0241

GnomAD4 genome AF: 0.0173 AC: 2630 AN: 151736 Hom.: 235 Cov.: 32 AF XY: 0.0229 AC XY: 1695 AN XY: 74132

Gnomad4 AFR AF: 0.00283

Gnomad4 AMR AF: 0.0362

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.0448

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.0226

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.0285

Alfa AF: 0.00187 Hom.: 0

Bravo AF: 0.0122

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	-0.90
CADD	Benign	1.3
DANN	Benign	0.52

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: rs1887416; hg19: chr6-137518962;