NM_000416.3:c.*206A>G

Variant names:

• chr6-137197825-T-C
• rs1887416
• NM_000416.3:c.*206A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000416.3(IFNGR1):​c.*206A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 566,144 control chromosomes in the GnomAD database, including 1,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (235 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1630 hom.)
• Consequence: IFNGR1 NM_000416.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00400
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-137197825-T-C is Benign according to our data. Variant chr6-137197825-T-C is described in ClinVar as Benign. ClinVar VariationId is 355549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 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.*206A>G		3_prime_UTR	Exon 7 of 7	NP_000407.1	A0A0S2Z3Y2
	IFNGR1	NM_001363526.1		c.*206A>G		3_prime_UTR	Exon 8 of 8	NP_001350455.1	A0A2R8Y4U4
	IFNGR1	NM_001363527.1		c.*206A>G		3_prime_UTR	Exon 7 of 7	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.*206A>G		3_prime_UTR	Exon 7 of 7	ENSP00000356713.5	P15260-1
	IFNGR1	ENST00000957752.1		c.*206A>G		3_prime_UTR	Exon 7 of 7	ENSP00000627811.1
	IFNGR1	ENST00000414770.6	TSL:3	c.*206A>G		3_prime_UTR	Exon 8 of 8	ENSP00000394230.2	A0A2R8Y4U4

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2609 AN: 151620 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.00284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.0443

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.0226

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0216

GnomAD4 exome AF: 0.0335 AC: 13891 AN: 414408 Hom.: 1630 Cov.: 5 AF XY: 0.0458 AC XY: 10101 AN XY: 220400

African (AFR) AF: 0.00163 AC: 19 AN: 11630

American (AMR) AF: 0.0577 AC: 936 AN: 16210

Ashkenazi Jewish (ASJ) AF: 0.00453 AC: 53 AN: 11708

East Asian (EAS) AF: 0.0310 AC: 759 AN: 24516

South Asian (SAS) AF: 0.252 AC: 10948 AN: 43420

European-Finnish (FIN) AF: 0.0162 AC: 332 AN: 20552

Middle Eastern (MID) AF: 0.00526 AC: 9 AN: 1710

European-Non Finnish (NFE) AF: 0.00110 AC: 287 AN: 261952

Other (OTH) AF: 0.0241 AC: 548 AN: 22710

GnomAD4 genome AF: 0.0173 AC: 2630 AN: 151736 Hom.: 235 Cov.: 32 AF XY: 0.0229 AC XY: 1695 AN XY: 74132

African (AFR) AF: 0.00283 AC: 117 AN: 41342

American (AMR) AF: 0.0362 AC: 552 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.0448 AC: 232 AN: 5180

South Asian (SAS) AF: 0.277 AC: 1332 AN: 4802

European-Finnish (FIN) AF: 0.0226 AC: 237 AN: 10466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 67930

Other (OTH) AF: 0.0285 AC: 60 AN: 2102

Alfa AF: 0.00187 Hom.: 0

Bravo AF: 0.0122

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 27A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-0.0040
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: rs1887416; hg19: chr6-137518962;