Variant 6-137197990-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000416.3(IFNGR1):c.*41G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,612,754 control chromosomes in the GnomAD database, including 163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0088 ( 13 hom., cov: 32)

Exomes 𝑓: 0.010 ( 150 hom. )

Consequence

IFNGR1
NM_000416.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.41

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-137197990-C-T is Benign according to our data. Variant chr6-137197990-C-T is described in ClinVar as [Benign]. Clinvar id is 907652.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00883 (1344/152210) while in subpopulation SAS AF= 0.0276 (133/4824). AF 95% confidence interval is 0.0238. There are 13 homozygotes in gnomad4. There are 696 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR1	NM_000416.3 linkuse as main transcript	c.*41G>A		3_prime_UTR_variant	7/7	ENST00000367739.9	NP_000407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNGR1	ENST00000367739.9 linkuse as main transcript	c.*41G>A		3_prime_UTR_variant	7/7	1	NM_000416.3	ENSP00000356713	P2	P15260-1

Frequencies

GnomAD3 genomes

AF:

0.00884

AC:

1345

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00858

Gnomad ASJ

AF:

0.0597

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0275

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00923

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0125

AC:

3137

AN:

250400

Hom.:

AF XY:

0.0139

AC XY:

1878

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00144

Gnomad AMR exome

AF:

0.00707

Gnomad ASJ exome

AF:

0.0581

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0283

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.00977

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0101

AC:

14802

AN:

1460544

Hom.:

150

Cov.:

AF XY:

0.0107

AC XY:

7807

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00734

Gnomad4 ASJ exome

AF:

0.0570

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0290

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.00811

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.00883

AC:

1344

AN:

152210

Hom.:

Cov.:

AF XY:

0.00935

AC XY:

696

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00857

Gnomad4 ASJ

AF:

0.0597

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0276

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.00923

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.00770

Asia WGS

AF:

0.00954

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency 27A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.2

DANN

Benign

0.70

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over