rs17882748

Positions:

• chr21-33403415-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR2	NM_005534.4	c.-129T>C		5_prime_UTR_variant	1/7	ENST00000290219.11
IFNGR2	NM_001329128.2	c.-129T>C		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR2	ENST00000290219.11	c.-129T>C		5_prime_UTR_variant	1/7	1	NM_005534.4	P1
IFNGR2	ENST00000381995.5			upstream_gene_variant		5
IFNGR2	ENST00000439213.5			upstream_gene_variant		5
IFNGR2	ENST00000545369.2			upstream_gene_variant		5

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

Gnomad4 AFR exome AF: 0.909

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.577

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

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.609

Alfa AF: 0.582 Hom.: 3334

Bravo AF: 0.646

Asia WGS AF: 0.656 AC: 2009 AN: 3070

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.7
DANN	Benign	0.47

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: rs17882748; hg19: chr21-34775721;