NM_000416.3:c.*71G>T

Variant names:

• chr6-137197960-C-A
• rs55665036
• NM_000416.3:c.*71G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000416.3(IFNGR1):​c.*71G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,600,442 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (111 hom.)
• Consequence: IFNGR1 NM_000416.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.528
• Publications: 1 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=-0.77).
• BP6: Variant 6-137197960-C-A is Benign according to our data. Variant chr6-137197960-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 355551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00829 (1262/152214) while in subpopulation NFE AF = 0.0113 (769/68020). AF 95% confidence interval is 0.0106. There are 7 homozygotes in GnomAd4. There are 649 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AD,AR gene

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.*71G>T		3_prime_UTR	Exon 7 of 7	NP_000407.1	A0A0S2Z3Y2
	IFNGR1	NM_001363526.1		c.*71G>T		3_prime_UTR	Exon 8 of 8	NP_001350455.1	A0A2R8Y4U4
	IFNGR1	NM_001363527.1		c.*71G>T		3_prime_UTR	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.*71G>T		3_prime_UTR	Exon 7 of 7	ENSP00000356713.5	P15260-1
	IFNGR1	ENST00000957752.1		c.*71G>T		3_prime_UTR	Exon 7 of 7	ENSP00000627811.1
	IFNGR1	ENST00000414770.6	TSL:3	c.*71G>T		3_prime_UTR	Exon 8 of 8	ENSP00000394230.2	A0A2R8Y4U4

Frequencies

GnomAD3 genomes AF: 0.00832 AC: 1265 AN: 152098 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.0114 AC: 16478 AN: 1448228 Hom.: 111 Cov.: 29 AF XY: 0.0114 AC XY: 8209 AN XY: 721180

African (AFR) AF: 0.00150 AC: 50 AN: 33230

American (AMR) AF: 0.00451 AC: 201 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00426 AC: 111 AN: 26050

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39608

South Asian (SAS) AF: 0.00949 AC: 808 AN: 85158

European-Finnish (FIN) AF: 0.0258 AC: 1360 AN: 52770

Middle Eastern (MID) AF: 0.00429 AC: 24 AN: 5598

European-Non Finnish (NFE) AF: 0.0121 AC: 13280 AN: 1101292

Other (OTH) AF: 0.0107 AC: 641 AN: 59932

GnomAD4 genome AF: 0.00829 AC: 1262 AN: 152214 Hom.: 7 Cov.: 32 AF XY: 0.00872 AC XY: 649 AN XY: 74416

African (AFR) AF: 0.00156 AC: 65 AN: 41538

American (AMR) AF: 0.00629 AC: 96 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00994 AC: 48 AN: 4828

European-Finnish (FIN) AF: 0.0231 AC: 245 AN: 10584

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0113 AC: 769 AN: 68020

Other (OTH) AF: 0.00996 AC: 21 AN: 2108

Alfa AF: 0.0107 Hom.: 2

Bravo AF: 0.00685

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 27A (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.3
DANN	Benign	0.74
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism

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: rs55665036; hg19: chr6-137519097;