GeneBe

12-68158261-TAAAAAAAA-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000619.3(IFNG):​c.115-10_115-3delTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000828 in 1,208,144 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

IFNG
NM_000619.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.416

Publications

0 publications found
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)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFNGNM_000619.3 linkc.115-10_115-3delTTTTTTTT splice_region_variant, intron_variant Intron 1 of 3 ENST00000229135.4 NP_000610.2 P01579A0A7R8GUN6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFNGENST00000229135.4 linkc.115-10_115-3delTTTTTTTT splice_region_variant, intron_variant Intron 1 of 3 1 NM_000619.3 ENSP00000229135.3 P01579
IFNG-AS1ENST00000536914.1 linkn.337-76267_337-76260delAAAAAAAA intron_variant Intron 5 of 5 5

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
8.28e-7
AC:
1
AN:
1208144
Hom.:
0
AF XY:
0.00000166
AC XY:
1
AN XY:
602032
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
24580
American (AMR)
AF:
0.00
AC:
0
AN:
28086
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20930
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36048
South Asian (SAS)
AF:
0.00
AC:
0
AN:
64332
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
43920
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4704
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
935564
Other (OTH)
AF:
0.0000200
AC:
1
AN:
49980
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2234686; hg19: chr12-68552041; API