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. The variant received -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
• Publications: 19 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=-0.87).
• BP6: Variant 21-33427043-C-G is Benign according to our data. Variant chr21-33427043-C-G is described in ClinVar as Benign. ClinVar VariationId is 402963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 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.561+11C>G		intron	N/A	NP_005525.2
	IFNGR2	NM_001329128.2		c.618+11C>G		intron	N/A	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.561+11C>G		intron	N/A	ENSP00000290219.5	P38484
	IFNGR2	ENST00000964420.1		c.711+11C>G		intron	N/A	ENSP00000634479.1
	IFNGR2	ENST00000897490.1		c.654+11C>G		intron	N/A	ENSP00000567549.1

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

GnomAD2 exomes AF: 0.769 AC: 192779 AN: 250840 AF XY: 0.760

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 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

African (AFR) AF: 0.868 AC: 28895 AN: 33284

American (AMR) AF: 0.852 AC: 38090 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 16790 AN: 26074

East Asian (EAS) AF: 0.978 AC: 38815 AN: 39682

South Asian (SAS) AF: 0.764 AC: 65726 AN: 86036

European-Finnish (FIN) AF: 0.790 AC: 42175 AN: 53384

Middle Eastern (MID) AF: 0.682 AC: 3917 AN: 5746

European-Non Finnish (NFE) AF: 0.700 AC: 773721 AN: 1104692

Other (OTH) AF: 0.735 AC: 44171 AN: 60082

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

African (AFR) AF: 0.864 AC: 35824 AN: 41452

American (AMR) AF: 0.814 AC: 12387 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2235 AN: 3464

East Asian (EAS) AF: 0.985 AC: 5086 AN: 5166

South Asian (SAS) AF: 0.774 AC: 3732 AN: 4820

European-Finnish (FIN) AF: 0.798 AC: 8397 AN: 10522

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47405 AN: 67976

Other (OTH) AF: 0.744 AC: 1562 AN: 2100

Alfa AF: 0.724 Hom.: 7369

Bravo AF: 0.781

Asia WGS AF: 0.890 AC: 3097 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency 28 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.65
DANN	Benign	0.51
PhyloP100		-0.031
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11910627; hg19: chr21-34799350;