rs9376268

chr6-137211614-G-Achr6-137211614-G-C

Variant summary

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

The NM_000416.3(IFNGR1):c.86-4537C>T 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 152,074 control chromosomes in the GnomAD database, including 3,472 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 (3472 hom., cov: 32)
• 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR1	NM_000416.3	c.86-4537C>T		intron_variant		ENST00000367739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR1	ENST00000367739.9	c.86-4537C>T		intron_variant		1	NM_000416.3	P2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30447 AN: 151956 Hom.: 3465 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.200 AC: 30484 AN: 152074 Hom.: 3472 Cov.: 32 AF XY: 0.203 AC XY: 15093 AN XY: 74370

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.206

Alfa AF: 0.230 Hom.: 5555

Bravo AF: 0.193

Asia WGS AF: 0.277 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.2
Dann	Benign	0.85

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: rs9376268; hg19: chr6-137532751; COSMIC: COSV62990275;