rs9376268

Variant names:

• chr6-137211614-G-A
• rs9376268
• NM_000416.3:c.86-4537C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-137211614-G-A
• chr6-137211614-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• immunodeficiency 27A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR1	NM_000416.3	MANE Select	c.86-4537C>T		intron	N/A	NP_000407.1	A0A0S2Z3Y2
	IFNGR1	NM_001363526.1		c.55+3653C>T		intron	N/A	NP_001350455.1	A0A2R8Y4U4
	IFNGR1	NM_001363527.1		c.-38-4537C>T		intron	N/A	NP_001350456.1	A0A2R8YFL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR1	ENST00000367739.9	TSL:1 MANE Select	c.86-4537C>T		intron	N/A	ENSP00000356713.5	P15260-1
	IFNGR1	ENST00000957752.1		c.86-4537C>T		intron	N/A	ENSP00000627811.1
	IFNGR1	ENST00000414770.6	TSL:3	c.55+3653C>T		intron	N/A	ENSP00000394230.2	A0A2R8Y4U4

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

African (AFR) AF: 0.0996 AC: 4136 AN: 41524

American (AMR) AF: 0.215 AC: 3284 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2063 AN: 5146

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4820

European-Finnish (FIN) AF: 0.212 AC: 2240 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 62 AN: 290

European-Non Finnish (NFE) AF: 0.234 AC: 15877 AN: 67964

Other (OTH) AF: 0.206 AC: 434 AN: 2110

Alfa AF: 0.225 Hom.: 6806

Bravo AF: 0.193

Asia WGS AF: 0.277 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.2
DANN	Benign	0.85
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: rs9376268; hg19: chr6-137532751; COSMIC: COSV62990275;