21-33437386-C-T

Variant names:

• chr21-33437386-C-T
• rs1059293
• NM_005534.4:c.*424C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005534.4(IFNGR2):​c.*424C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 179,596 control chromosomes in the GnomAD database, including 32,060 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 0.59 (28045 hom., cov: 32)
  • Exomes 𝑓: 0.53 (4015 hom.)
• Consequence: IFNGR2 NM_005534.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 65 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]

TMEM50B (HGNC:1280): (transmembrane protein 50B) Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 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.*424C>T		3_prime_UTR	Exon 7 of 7	NP_005525.2
	IFNGR2	NM_001329128.2		c.*424C>T		3_prime_UTR	Exon 8 of 8	NP_001316057.1	E7EUY1
	TMEM50B	NR_040016.2		n.2775+1828G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR2	ENST00000290219.11	TSL:1 MANE Select	c.*424C>T		3_prime_UTR	Exon 7 of 7	ENSP00000290219.5	P38484
	TMEM50B	ENST00000420455.5	TSL:1	n.*2120+1828G>A		intron	N/A	ENSP00000397773.1	P56557
	IFNGR2	ENST00000964420.1		c.*424C>T		3_prime_UTR	Exon 9 of 9	ENSP00000634479.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88846 AN: 151894 Hom.: 27999 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.526 AC: 14497 AN: 27584 Hom.: 4015 Cov.: 0 AF XY: 0.530 AC XY: 7564 AN XY: 14272

African (AFR) AF: 0.844 AC: 358 AN: 424

American (AMR) AF: 0.613 AC: 1546 AN: 2522

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 252 AN: 546

East Asian (EAS) AF: 0.842 AC: 1150 AN: 1366

South Asian (SAS) AF: 0.563 AC: 2151 AN: 3820

European-Finnish (FIN) AF: 0.513 AC: 571 AN: 1112

Middle Eastern (MID) AF: 0.407 AC: 22 AN: 54

European-Non Finnish (NFE) AF: 0.472 AC: 7676 AN: 16250

Other (OTH) AF: 0.517 AC: 771 AN: 1490

GnomAD4 genome AF: 0.585 AC: 88944 AN: 152012 Hom.: 28045 Cov.: 32 AF XY: 0.587 AC XY: 43617 AN XY: 74298

African (AFR) AF: 0.811 AC: 33653 AN: 41496

American (AMR) AF: 0.578 AC: 8822 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1549 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4270 AN: 5174

South Asian (SAS) AF: 0.575 AC: 2773 AN: 4820

European-Finnish (FIN) AF: 0.510 AC: 5379 AN: 10552

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30907 AN: 67930

Other (OTH) AF: 0.527 AC: 1113 AN: 2112

Alfa AF: 0.501 Hom.: 58976

Bravo AF: 0.603

Asia WGS AF: 0.700 AC: 2434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.17
DANN	Benign	0.78
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1059293; hg19: chr21-34809693;