6-137199749-C-T

Position:

• chr6-137199749-C-T

Variant summary

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

The NM_000416.3(IFNGR1):​c.862-1110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 148,240 control chromosomes in the GnomAD database, including 3,418 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 0.20 (3418 hom., cov: 29)
• Consequence: IFNGR1 NM_000416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.862-1110G>A		intron_variant		ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9	c.862-1110G>A		intron_variant		1	NM_000416.3	ENSP00000356713.5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 29636 AN: 148134 Hom.: 3410 Cov.: 29

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.200 AC: 29670 AN: 148240 Hom.: 3418 Cov.: 29 AF XY: 0.202 AC XY: 14560 AN XY: 71998

Gnomad4 AFR AF: 0.0985

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.202

Alfa AF: 0.213 Hom.: 443

Bravo AF: 0.194

Asia WGS AF: 0.275 AC: 946 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.0
DANN	Benign	0.82

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: rs56251346; hg19: chr6-137520886;