rs2234711

Variant names:

• chr6-137219383-A-G
• rs2234711
• NM_000416.3:c.-56T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-137219383-A-G
• chr6-137219383-A-C
• chr6-137219383-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000416.3(IFNGR1):​c.-56T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,561,786 control chromosomes in the GnomAD database, including 134,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14831 hom., cov: 33)
  • Exomes 𝑓: 0.41 (120067 hom.)
• Consequence: IFNGR1 NM_000416.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:2
• Conservation: PhyloP100: 0.0900
• Publications: 97 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-137219383-A-G is Benign according to our data. Variant chr6-137219383-A-G is described in ClinVar as Benign. ClinVar VariationId is 355565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.61 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.-56T>C		5_prime_UTR	Exon 1 of 7	NP_000407.1	A0A0S2Z3Y2
	IFNGR1	NM_001363526.1		c.-456T>C		upstream_gene	N/A	NP_001350455.1	A0A2R8Y4U4
	IFNGR1	NM_001363527.1		c.-750T>C		upstream_gene	N/A	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.-56T>C		5_prime_UTR	Exon 1 of 7	ENSP00000356713.5	P15260-1
	IFNGR1	ENST00000957752.1		c.-56T>C		5_prime_UTR	Exon 1 of 7	ENSP00000627811.1
	IFNGR1	ENST00000414770.6	TSL:3	c.-197T>C		5_prime_UTR	Exon 1 of 8	ENSP00000394230.2	A0A2R8Y4U4

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66223 AN: 151998 Hom.: 14787 Cov.: 33

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.407 AC: 573788 AN: 1409670 Hom.: 120067 Cov.: 41 AF XY: 0.413 AC XY: 287672 AN XY: 696240

African (AFR) AF: 0.516 AC: 16724 AN: 32418

American (AMR) AF: 0.368 AC: 13338 AN: 36290

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12482 AN: 25196

East Asian (EAS) AF: 0.540 AC: 19953 AN: 36946

South Asian (SAS) AF: 0.605 AC: 48455 AN: 80096

European-Finnish (FIN) AF: 0.366 AC: 18129 AN: 49528

Middle Eastern (MID) AF: 0.508 AC: 2851 AN: 5614

European-Non Finnish (NFE) AF: 0.384 AC: 416287 AN: 1085168

Other (OTH) AF: 0.438 AC: 25569 AN: 58414

GnomAD4 genome AF: 0.436 AC: 66326 AN: 152116 Hom.: 14831 Cov.: 33 AF XY: 0.439 AC XY: 32676 AN XY: 74364

African (AFR) AF: 0.506 AC: 21008 AN: 41508

American (AMR) AF: 0.394 AC: 6032 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2975 AN: 5156

South Asian (SAS) AF: 0.628 AC: 3031 AN: 4824

European-Finnish (FIN) AF: 0.353 AC: 3740 AN: 10580

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.387 AC: 26279 AN: 67972

Other (OTH) AF: 0.472 AC: 995 AN: 2108

Alfa AF: 0.643 Hom.: 8010

Bravo AF: 0.435

Asia WGS AF: 0.631 AC: 2191 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Disseminated atypical mycobacterial infection (1)
-	-	1	Immunodeficiency 27A (1)
-	-	1	not specified (1)
-	-	-	Helicobacter pylori infection, susceptibility to (1)
-	-	-	Hepatitis B virus, susceptibility to (1)
-	-	-	Mycobacterium tuberculosis, protection against (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.57
PhyloP100		0.090
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2234711; hg19: chr6-137540520; COSMIC: COSV62990213; COSMIC: COSV62990213;