rs17882748

Variant names:

• chr21-33403415-T-C
• rs17882748
• NM_005534.4:c.-129T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005534.4(IFNGR2):​c.-129T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 380,554 control chromosomes in the GnomAD database, including 66,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31898 hom., cov: 31)
  • Exomes 𝑓: 0.54 (34657 hom.)
• Consequence: IFNGR2 NM_005534.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.619
• Publications: 11 publications found

Genes affected

IFNGR2 (HGNC:5440): (interferon gamma receptor 2) This gene (IFNGR2) encodes the non-ligand-binding beta chain of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. Defects in IFNGR2 are a cause of mendelian susceptibility to mycobacterial disease (MSMD), also known as familial disseminated atypical mycobacterial infection. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. [provided by RefSeq, Jul 2008]

IFNGR2 Gene-Disease associations (from GenCC):

• immunodeficiency 28

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 21-33403415-T-C is Benign according to our data. Variant chr21-33403415-T-C is described in ClinVar as Benign. ClinVar VariationId is 1277058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005534.4. 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
	IFNGR2	NM_005534.4	MANE Select	c.-129T>C		5_prime_UTR	Exon 1 of 7	NP_005525.2
	IFNGR2	NM_001329128.2		c.-129T>C		5_prime_UTR	Exon 1 of 8	NP_001316057.1	E7EUY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR2	ENST00000290219.11	TSL:1 MANE Select	c.-129T>C		5_prime_UTR	Exon 1 of 7	ENSP00000290219.5	P38484
	IFNGR2	ENST00000964419.1		c.-129T>C		5_prime_UTR	Exon 1 of 5	ENSP00000634478.1
	IFNGR2	ENST00000964420.1		c.-129T>C		upstream_gene	N/A	ENSP00000634479.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 94861 AN: 150108 Hom.: 31852 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.541 AC: 124630 AN: 230336 Hom.: 34657 Cov.: 5 AF XY: 0.540 AC XY: 61183 AN XY: 113278

African (AFR) AF: 0.909 AC: 4155 AN: 4570

American (AMR) AF: 0.507 AC: 997 AN: 1966

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1360 AN: 2502

East Asian (EAS) AF: 0.624 AC: 2092 AN: 3354

South Asian (SAS) AF: 0.644 AC: 3102 AN: 4814

European-Finnish (FIN) AF: 0.494 AC: 2965 AN: 5996

Middle Eastern (MID) AF: 0.535 AC: 355 AN: 664

European-Non Finnish (NFE) AF: 0.529 AC: 104484 AN: 197600

Other (OTH) AF: 0.577 AC: 5120 AN: 8870

GnomAD4 genome AF: 0.632 AC: 94957 AN: 150218 Hom.: 31898 Cov.: 31 AF XY: 0.629 AC XY: 46089 AN XY: 73310

African (AFR) AF: 0.884 AC: 36494 AN: 41274

American (AMR) AF: 0.559 AC: 8438 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1887 AN: 3440

East Asian (EAS) AF: 0.593 AC: 3016 AN: 5082

South Asian (SAS) AF: 0.629 AC: 3035 AN: 4824

European-Finnish (FIN) AF: 0.503 AC: 5019 AN: 9970

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35297 AN: 67244

Other (OTH) AF: 0.609 AC: 1267 AN: 2082

Alfa AF: 0.582 Hom.: 3334

Bravo AF: 0.646

Asia WGS AF: 0.656 AC: 2009 AN: 3070

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.7
DANN	Benign	0.47
PhyloP100		0.62
PromoterAI		0.078	Neutral
Mutation Taster		=298/2	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: rs17882748; hg19: chr21-34775721;