chr12-68155252-TTTGA-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_000619.3(IFNG):​c.*97_*100del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 760,522 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 8 hom. )

Consequence

IFNG
NM_000619.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2O:1

Conservation

PhyloP100: 0.908
Variant links:
Genes affected
IFNG (HGNC:5438): (interferon gamma) This gene encodes a soluble cytokine that is a member of the type II interferon class. The encoded protein is secreted by cells of both the innate and adaptive immune systems. The active protein is a homodimer that binds to the interferon gamma receptor which triggers a cellular response to viral and microbial infections. Mutations in this gene are associated with an increased susceptibility to viral, bacterial and parasitic infections and to several autoimmune diseases. [provided by RefSeq, Dec 2015]
IFNG-AS1 (HGNC:43910): (IFNG antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00143 (869/608186) while in subpopulation MID AF= 0.0194 (50/2582). AF 95% confidence interval is 0.0151. There are 8 homozygotes in gnomad4_exome. There are 426 alleles in male gnomad4_exome subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IFNGNM_000619.3 linkuse as main transcriptc.*97_*100del 3_prime_UTR_variant 4/4 ENST00000229135.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IFNGENST00000229135.4 linkuse as main transcriptc.*97_*100del 3_prime_UTR_variant 4/41 NM_000619.3 P1
IFNG-AS1ENST00000536914.1 linkuse as main transcriptn.337-79271_337-79268del intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00314
AC:
478
AN:
152218
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00622
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00622
Gnomad ASJ
AF:
0.0133
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000882
Gnomad OTH
AF:
0.00478
GnomAD4 exome
AF:
0.00143
AC:
869
AN:
608186
Hom.:
8
AF XY:
0.00138
AC XY:
426
AN XY:
309528
show subpopulations
Gnomad4 AFR exome
AF:
0.00755
Gnomad4 AMR exome
AF:
0.00401
Gnomad4 ASJ exome
AF:
0.0102
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000484
Gnomad4 FIN exome
AF:
0.0000317
Gnomad4 NFE exome
AF:
0.000933
Gnomad4 OTH exome
AF:
0.00307
GnomAD4 genome
AF:
0.00314
AC:
479
AN:
152336
Hom.:
1
Cov.:
32
AF XY:
0.00294
AC XY:
219
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.00623
Gnomad4 AMR
AF:
0.00621
Gnomad4 ASJ
AF:
0.0133
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000828
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000882
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00276
Hom.:
0
Bravo
AF:
0.00389
Asia WGS
AF:
0.00116
AC:
4
AN:
3464

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1Other:1
not provided, no classification providedliterature onlyHuman Evolutionary Genetics, Institut Pasteur-- -
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Aplastic anemia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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.

Other links and lift over

dbSNP: rs137854903; hg19: chr12-68549032; API