6-137199749-C-T

Variant names:

• chr6-137199749-C-T
• rs56251346
• NM_000416.3:c.862-1110G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

IFNGR1 Gene-Disease associations (from GenCC):

• autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• immunodeficiency 27A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.862-1110G>A		intron_variant	Intron 6 of 6	ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9	c.862-1110G>A		intron_variant	Intron 6 of 6	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

African (AFR) AF: 0.0985 AC: 3971 AN: 40322

American (AMR) AF: 0.209 AC: 3008 AN: 14358

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 910 AN: 3458

East Asian (EAS) AF: 0.408 AC: 2062 AN: 5048

South Asian (SAS) AF: 0.261 AC: 1244 AN: 4770

European-Finnish (FIN) AF: 0.209 AC: 2019 AN: 9642

Middle Eastern (MID) AF: 0.212 AC: 61 AN: 288

European-Non Finnish (NFE) AF: 0.234 AC: 15779 AN: 67428

Other (OTH) AF: 0.202 AC: 411 AN: 2034

Alfa AF: 0.208 Hom.: 446

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
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56251346; hg19: chr6-137520886;