chr6-137218368-C-G

Position:

• chr6-137218368-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000416.3(IFNGR1):​c.85+875G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 640,188 control chromosomes in the GnomAD database, including 26,551 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4529 hom., cov: 32)
  • Exomes 𝑓: 0.28 (22022 hom.)
• Consequence: IFNGR1 NM_000416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.85+875G>C		intron_variant		ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9	c.85+875G>C		intron_variant		1	NM_000416.3	ENSP00000356713	P2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34671 AN: 151914 Hom.: 4509 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.280 AC: 136738 AN: 488154 Hom.: 22022 AF XY: 0.298 AC XY: 77550 AN XY: 260552

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.522

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.228 AC: 34732 AN: 152034 Hom.: 4529 Cov.: 32 AF XY: 0.236 AC XY: 17533 AN XY: 74314

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.238

Alfa AF: 0.225 Hom.: 476

Bravo AF: 0.218

Asia WGS AF: 0.495 AC: 1716 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
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: rs9376269; hg19: chr6-137539505;