6-137197960-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000416.3(IFNGR1):c.*71G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,600,442 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (111 hom.)
• Consequence: IFNGR1 NM_000416.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.528

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=-0.77).
• BP6: Variant 6-137197960-C-A is Benign according to our data. Variant chr6-137197960-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 355551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00829 (1262/152214) while in subpopulation NFE AF= 0.0113 (769/68020). AF 95% confidence interval is 0.0106. There are 7 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR1	NM_000416.3	c.*71G>T		3_prime_UTR_variant	7/7	ENST00000367739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR1	ENST00000367739.9	c.*71G>T		3_prime_UTR_variant	7/7	1	NM_000416.3	P2

Frequencies

GnomAD3 genomes AF: 0.00832 AC: 1265 AN: 152098 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.0114 AC: 16478 AN: 1448228 Hom.: 111 Cov.: 29 AF XY: 0.0114 AC XY: 8209 AN XY: 721180

Gnomad4 AFR exome AF: 0.00150

Gnomad4 AMR exome AF: 0.00451

Gnomad4 ASJ exome AF: 0.00426

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00949

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.00829 AC: 1262 AN: 152214 Hom.: 7 Cov.: 32 AF XY: 0.00872 AC XY: 649 AN XY: 74416

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00629

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.00996

Alfa AF: 0.0107 Hom.: 2

Bravo AF: 0.00685

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency 27A Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	5.3
Dann	Benign	0.74

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: rs55665036; hg19: chr6-137519097;