rs11914

Variant names:

• chr6-137198451-A-C
• rs11914
• NM_000416.3:c.1050T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-137198451-A-C
• chr6-137198451-A-G
• chr6-137198451-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000416.3(IFNGR1):​c.1050T>G​(p.Ser350Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,614,050 control chromosomes in the GnomAD database, including 18,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1340 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17198 hom.)
• Consequence: IFNGR1 NM_000416.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -0.671
• Publications: 37 publications found

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]

IFNGR1 Gene-Disease associations (from GenCC):

• autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• immunodeficiency 27A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-137198451-A-C is Benign according to our data. Variant chr6-137198451-A-C is described in ClinVar as Benign. ClinVar VariationId is 355554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.671 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000416.3. 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
	IFNGR1	NM_000416.3	MANE Select	c.1050T>G	p.Ser350Ser	synonymous	Exon 7 of 7	NP_000407.1	A0A0S2Z3Y2
	IFNGR1	NM_001363526.1		c.1020T>G	p.Ser340Ser	synonymous	Exon 8 of 8	NP_001350455.1	A0A2R8Y4U4
	IFNGR1	NM_001363527.1		c.927T>G	p.Ser309Ser	synonymous	Exon 7 of 7	NP_001350456.1	A0A2R8YFL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR1	ENST00000367739.9	TSL:1 MANE Select	c.1050T>G	p.Ser350Ser	synonymous	Exon 7 of 7	ENSP00000356713.5	P15260-1
	IFNGR1	ENST00000957752.1		c.1044T>G	p.Ser348Ser	synonymous	Exon 7 of 7	ENSP00000627811.1
	IFNGR1	ENST00000414770.6	TSL:3	c.1020T>G	p.Ser340Ser	synonymous	Exon 8 of 8	ENSP00000394230.2	A0A2R8Y4U4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18983 AN: 152062 Hom.: 1336 Cov.: 31

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.132 AC: 33088 AN: 251366 AF XY: 0.134

Gnomad AFR exome AF: 0.0632

Gnomad AMR exome AF: 0.0850

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.149 AC: 218495 AN: 1461870 Hom.: 17198 Cov.: 33 AF XY: 0.149 AC XY: 108160 AN XY: 727242

African (AFR) AF: 0.0626 AC: 2097 AN: 33480

American (AMR) AF: 0.0886 AC: 3961 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5586 AN: 26136

East Asian (EAS) AF: 0.0856 AC: 3397 AN: 39700

South Asian (SAS) AF: 0.0868 AC: 7490 AN: 86258

European-Finnish (FIN) AF: 0.113 AC: 6022 AN: 53412

Middle Eastern (MID) AF: 0.187 AC: 1076 AN: 5768

European-Non Finnish (NFE) AF: 0.162 AC: 179742 AN: 1112004

Other (OTH) AF: 0.151 AC: 9124 AN: 60396

GnomAD4 genome AF: 0.125 AC: 18983 AN: 152180 Hom.: 1340 Cov.: 31 AF XY: 0.121 AC XY: 9024 AN XY: 74422

African (AFR) AF: 0.0653 AC: 2711 AN: 41526

American (AMR) AF: 0.110 AC: 1678 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3472

East Asian (EAS) AF: 0.119 AC: 619 AN: 5186

South Asian (SAS) AF: 0.0898 AC: 433 AN: 4822

European-Finnish (FIN) AF: 0.104 AC: 1099 AN: 10596

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11143 AN: 68002

Other (OTH) AF: 0.148 AC: 313 AN: 2108

Alfa AF: 0.149 Hom.: 1717

Bravo AF: 0.124

Asia WGS AF: 0.104 AC: 363 AN: 3478

EpiCase AF: 0.184

EpiControl AF: 0.189

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Disseminated atypical mycobacterial infection (1)
-	-	1	Immunodeficiency 27A (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.44
PhyloP100		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11914; hg19: chr6-137519588; COSMIC: COSV62992002;