6-137206316-GAATA-G

Variant names:

• chr6-137206316-GAATA-G
• rs766023933
• NM_000416.3:c.201-12_201-9delTATT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_000416.3(IFNGR1):​c.201-12_201-9delTATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,582,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: IFNGR1 NM_000416.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.42
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• immunodeficiency 27A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 6-137206316-GAATA-G is Benign according to our data. Variant chr6-137206316-GAATA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 531673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000322 (46/1430712) while in subpopulation AMR AF = 0.000566 (25/44192). AF 95% confidence interval is 0.000393. There are 0 homozygotes in GnomAdExome4. There are 23 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR1	NM_000416.3	MANE Select	c.201-12_201-9delTATT		intron	N/A	NP_000407.1
	IFNGR1	NM_001363526.1		c.171-12_171-9delTATT		intron	N/A	NP_001350455.1
	IFNGR1	NM_001363527.1		c.78-12_78-9delTATT		intron	N/A	NP_001350456.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR1	ENST00000367739.9	TSL:1 MANE Select	c.201-12_201-9delTATT		intron	N/A	ENSP00000356713.5
	IFNGR1	ENST00000414770.6	TSL:3	c.171-12_171-9delTATT		intron	N/A	ENSP00000394230.2
	IFNGR1	ENST00000646036.1		c.171-12_171-9delTATT		intron	N/A	ENSP00000496387.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 151982 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000101 AC: 25 AN: 247548 AF XY: 0.0000968

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000557

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000446

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000322 AC: 46 AN: 1430712 Hom.: 0 AF XY: 0.0000322 AC XY: 23 AN XY: 713220

African (AFR) AF: 0.0000612 AC: 2 AN: 32674

American (AMR) AF: 0.000566 AC: 25 AN: 44192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.00 AC: 0 AN: 85054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.0000138 AC: 15 AN: 1084996

Other (OTH) AF: 0.0000674 AC: 4 AN: 59364

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152100 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41484

American (AMR) AF: 0.000458 AC: 7 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67974

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000480 Hom.: 0

Bravo AF: 0.0000718

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Disseminated atypical mycobacterial infection Benign:1

Nov 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

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: rs766023933; hg19: chr6-137527453;