rs1327475

Positions:

• chr6-137215318-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000416.3(IFNGR1):​c.85+3925C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,545,614 control chromosomes in the GnomAD database, including 17,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1297 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16300 hom.)
• Consequence: IFNGR1 NM_000416.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.447

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015720427).
• BP6: Variant 6-137215318-G-A is Benign according to our data. Variant chr6-137215318-G-A is described in ClinVar as [Benign]. Clinvar id is 2688498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR1	NM_000416.3	c.85+3925C>T		intron_variant		ENST00000367739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR1	ENST00000367739.9	c.85+3925C>T		intron_variant		1	NM_000416.3	P2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18582 AN: 152046 Hom.: 1294 Cov.: 32

Gnomad AFR AF: 0.0581

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.128 AC: 18943 AN: 147932 Hom.: 1391 AF XY: 0.128 AC XY: 10206 AN XY: 79680

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.0863

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.124

Gnomad SAS exome AF: 0.0839

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.149 AC: 206939 AN: 1393450 Hom.: 16300 Cov.: 31 AF XY: 0.148 AC XY: 101391 AN XY: 687266

Gnomad4 AFR exome AF: 0.0555

Gnomad4 AMR exome AF: 0.0896

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.0822

Gnomad4 SAS exome AF: 0.0848

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.122 AC: 18581 AN: 152164 Hom.: 1297 Cov.: 32 AF XY: 0.119 AC XY: 8842 AN XY: 74390

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0891

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.148

Alfa AF: 0.147 Hom.: 912

Bravo AF: 0.121

TwinsUK AF: 0.155 AC: 575

ALSPAC AF: 0.155 AC: 598

ExAC AF: 0.113 AC: 2065

Asia WGS AF: 0.104 AC: 360 AN: 3444

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	6.1
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	.;.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.27	.;T;T
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	1.0	P;P
PROVEAN	Benign	-0.52	.;.;N
REVEL	Benign	0.090
Sift	Pathogenic	0.0	.;.;D
ClinPred		0.011	T
GERP RS		1.4

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: rs1327475; hg19: chr6-137536455; COSMIC: COSV62990076;