6-137197814-A-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.*217T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 529,282 control chromosomes in the GnomAD database, including 1,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (210 hom., cov: 31)
  • Exomes 𝑓: 0.033 (1408 hom.)
• Consequence: IFNGR1 NM_000416.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.347

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=-0.84).
• BP6: Variant 6-137197814-A-T is Benign according to our data. Variant chr6-137197814-A-T is described in ClinVar as [Benign]. Clinvar id is 355548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR1	NM_000416.3	c.*217T>A		3_prime_UTR_variant	7/7	ENST00000367739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR1	ENST00000367739.9	c.*217T>A		3_prime_UTR_variant	7/7	1	NM_000416.3	P2

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2464 AN: 152032 Hom.: 207 Cov.: 31

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0436

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0173

GnomAD4 exome AF: 0.0335 AC: 12621 AN: 377134 Hom.: 1408 Cov.: 5 AF XY: 0.0454 AC XY: 9170 AN XY: 201818

Gnomad4 AFR exome AF: 0.00157

Gnomad4 AMR exome AF: 0.0586

Gnomad4 ASJ exome AF: 0.00450

Gnomad4 EAS exome AF: 0.0314

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.000783

Gnomad4 OTH exome AF: 0.0211

GnomAD4 genome AF: 0.0163 AC: 2477 AN: 152148 Hom.: 210 Cov.: 31 AF XY: 0.0217 AC XY: 1612 AN XY: 74374

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.0440

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.0225

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.00572 Hom.: 6

Bravo AF: 0.0117

Asia WGS AF: 0.169 AC: 584 AN: 3474

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	-0.84
Cadd	Benign	0.89
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1887417; hg19: chr6-137518951;