6-137218673-G-A

Position:

• chr6-137218673-G-A

Variant summary

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

The NM_001363527.1(IFNGR1):​c.-40C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 350,342 control chromosomes in the GnomAD database, including 5,516 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3109 hom., cov: 27)
  • Exomes 𝑓: 0.14 (2407 hom.)
• Consequence: IFNGR1 NM_001363527.1 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.85+570C>T		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+570C>T		intron_variant		1	NM_000416.3	ENSP00000356713.5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 28760 AN: 142324 Hom.: 3097 Cov.: 27

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.144 AC: 29849 AN: 207948 Hom.: 2407 Cov.: 3 AF XY: 0.136 AC XY: 15526 AN XY: 114086

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.0889

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.202 AC: 28796 AN: 142394 Hom.: 3109 Cov.: 27 AF XY: 0.200 AC XY: 13671 AN XY: 68186

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0961

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.227

Alfa AF: 0.162 Hom.: 1676

Bravo AF: 0.202

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.4
DANN	Benign	0.84

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: rs10457655; hg19: chr6-137539810; COSMIC: COSV62989439;