rs11910627

Variant names:

• chr21-33427043-C-G
• rs11910627
• NM_005534.4:c.561+11C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-33427043-C-G
• chr21-33427043-C-T

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.561+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,605,584 control chromosomes in the GnomAD database, including 430,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45896 hom., cov: 29)
  • Exomes 𝑓: 0.72 (384482 hom.)
• Consequence: IFNGR2 NM_005534.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0310

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=-0.87).
• BP6: Variant 21-33427043-C-G is Benign according to our data. Variant chr21-33427043-C-G is described in ClinVar as [Benign]. Clinvar id is 402963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-33427043-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR2	NM_005534.4	c.561+11C>G		intron_variant	Intron 4 of 6	ENST00000290219.11	NP_005525.2
IFNGR2	NM_001329128.2	c.618+11C>G		intron_variant	Intron 5 of 7		NP_001316057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR2	ENST00000290219.11	c.561+11C>G		intron_variant	Intron 4 of 6	1	NM_005534.4	ENSP00000290219.5

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117281 AN: 151802 Hom.: 45835 Cov.: 29

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.743

GnomAD3 exomes AF: 0.769 AC: 192779 AN: 250840 Hom.: 75344 AF XY: 0.760 AC XY: 103104 AN XY: 135596

Gnomad AFR exome AF: 0.871

Gnomad AMR exome AF: 0.859

Gnomad ASJ exome AF: 0.641

Gnomad EAS exome AF: 0.994

Gnomad SAS exome AF: 0.767

Gnomad FIN exome AF: 0.800

Gnomad NFE exome AF: 0.698

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.724 AC: 1052300 AN: 1453664 Hom.: 384482 Cov.: 32 AF XY: 0.723 AC XY: 523217 AN XY: 723656

Gnomad4 AFR exome AF: 0.868

Gnomad4 AMR exome AF: 0.852

Gnomad4 ASJ exome AF: 0.644

Gnomad4 EAS exome AF: 0.978

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.790

Gnomad4 NFE exome AF: 0.700

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.773 AC: 117400 AN: 151920 Hom.: 45896 Cov.: 29 AF XY: 0.780 AC XY: 57878 AN XY: 74228

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.744

Alfa AF: 0.724 Hom.: 7369

Bravo AF: 0.781

Asia WGS AF: 0.890 AC: 3097 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -

Immunodeficiency 28 Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.65
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11910627; hg19: chr21-34799350;