rs11575931

Variant names:

• chr6-137219280-C-A
• rs11575931
• NM_000416.3:c.48G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-137219280-C-A
• chr6-137219280-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000416.3(IFNGR1):​c.48G>T​(p.Arg16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IFNGR1 NM_000416.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

Genes affected

IFNGR1 (HGNC:5439): (interferon gamma receptor 1) This gene (IFNGR1) encodes the ligand-binding chain (alpha) of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. A genetic variation in IFNGR1 is associated with susceptibility to Helicobacter pylori infection. In addition, defects in IFNGR1 are a cause of mendelian susceptibility to mycobacterial disease, also known as familial disseminated atypical mycobacterial infection. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078030854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR1	NM_000416.3	c.48G>T	p.Arg16Ser	missense_variant	Exon 1 of 7	ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9	c.48G>T	p.Arg16Ser	missense_variant	Exon 1 of 7	1	NM_000416.3	ENSP00000356713.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000410 AC: 1 AN: 244084 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459636 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 725880

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.0065	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	2.8
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.070	N;N
REVEL	Benign	0.23
Sift	Benign	0.63	T;T
Sift4G	Benign	0.78	T;.
Polyphen		0.037	B;.
Vest4		0.067
MutPred		0.54		Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);
MVP		0.80
MPC		0.056
ClinPred		0.047	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.10
gMVP		0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs11575931; hg19: chr6-137540417;