6-137197990-C-T

Variant names:

• chr6-137197990-C-T
• rs17181562
• NM_000416.3:c.*41G>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.*41G>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 0.01 in 1,612,754 control chromosomes in the GnomAD database, including 163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (13 hom., cov: 32)
  • Exomes 𝑓: 0.010 (150 hom.)
• Consequence: IFNGR1 NM_000416.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.41

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=-0.78).
• BP6: Variant 6-137197990-C-T is Benign according to our data. Variant chr6-137197990-C-T is described in ClinVar as [Benign]. Clinvar id is 907652.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00883 (1344/152210) while in subpopulation SAS AF= 0.0276 (133/4824). AF 95% confidence interval is 0.0238. There are 13 homozygotes in gnomad4. There are 696 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.*41G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739	c.*41G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_000416.3	ENSP00000356713.5

Frequencies

GnomAD3 genomes AF: 0.00884 AC: 1345 AN: 152092 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00858

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00923

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0125 AC: 3137 AN: 250400 Hom.: 42 AF XY: 0.0139 AC XY: 1878 AN XY: 135524

Gnomad AFR exome AF: 0.00144

Gnomad AMR exome AF: 0.00707

Gnomad ASJ exome AF: 0.0581

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0283

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.00977

Gnomad OTH exome AF: 0.0153

GnomAD4 exome AF: 0.0101 AC: 14802 AN: 1460544 Hom.: 150 Cov.: 30 AF XY: 0.0107 AC XY: 7807 AN XY: 726650

Gnomad4 AFR exome AF: 0.00120

Gnomad4 AMR exome AF: 0.00734

Gnomad4 ASJ exome AF: 0.0570

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0290

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.00811

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.00883 AC: 1344 AN: 152210 Hom.: 13 Cov.: 32 AF XY: 0.00935 AC XY: 696 AN XY: 74420

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00857

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0276

Gnomad4 FIN AF: 0.0109

Gnomad4 NFE AF: 0.00923

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0116 Hom.: 17

Bravo AF: 0.00770

Asia WGS AF: 0.00954 AC: 33 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency 27A Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.78
CADD	Benign	3.2
DANN	Benign	0.70

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: rs17181562; hg19: chr6-137519127;