NM_005534.4:c.722-42C>T

Variant names:

• chr21-33432672-C-T
• rs121913216
• NM_005534.4:c.722-42C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005534.4(IFNGR2):​c.722-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,602,266 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00097 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (5 hom.)
• Consequence: IFNGR2 NM_005534.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.769
• Publications: 0 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).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000966 (147/152250) while in subpopulation NFE AF = 0.00175 (119/68028). AF 95% confidence interval is 0.00149. There are 0 homozygotes in GnomAd4. There are 72 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR,AD gene

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.722-42C>T		intron	N/A	NP_005525.2
	IFNGR2	NM_001329128.2		c.779-42C>T		intron	N/A	NP_001316057.1	E7EUY1
	TMEM50B	NR_040016.2		n.2906G>A		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR2	ENST00000290219.11	TSL:1 MANE Select	c.722-42C>T		intron	N/A	ENSP00000290219.5	P38484
	TMEM50B	ENST00000420455.5	TSL:1	n.*2251G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000397773.1	P56557
	TMEM50B	ENST00000420455.5	TSL:1	n.*2251G>A		3_prime_UTR	Exon 9 of 9	ENSP00000397773.1	P56557

Frequencies

GnomAD3 genomes AF: 0.000966 AC: 147 AN: 152132 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000850

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000908 AC: 228 AN: 251170 AF XY: 0.000928

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00141

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00151 AC: 2183 AN: 1450016 Hom.: 5 Cov.: 33 AF XY: 0.00144 AC XY: 1039 AN XY: 722110

African (AFR) AF: 0.000150 AC: 5 AN: 33272

American (AMR) AF: 0.000738 AC: 33 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86022

European-Finnish (FIN) AF: 0.00171 AC: 91 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00177 AC: 1951 AN: 1101202

Other (OTH) AF: 0.00162 AC: 97 AN: 60024

GnomAD4 genome AF: 0.000966 AC: 147 AN: 152250 Hom.: 0 Cov.: 31 AF XY: 0.000967 AC XY: 72 AN XY: 74438

African (AFR) AF: 0.000217 AC: 9 AN: 41538

American (AMR) AF: 0.000524 AC: 8 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000850 AC: 9 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00175 AC: 119 AN: 68028

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00119 Hom.: 0

Bravo AF: 0.000945

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.27
DANN	Benign	0.67
PhyloP100		-0.77
PromoterAI		-0.0090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs121913216; hg19: chr21-34804979;