NM_000619.3:c.115-5_115-3delTTT

Variant names:

• chr12-68158261-TAAA-T
• rs2234686
• NM_000619.3:c.115-5_115-3delTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000619.3(IFNG):​c.115-5_115-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000648 in 1,199,252 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00065 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFNG NM_000619.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 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
IFNG	NM_000619.3	c.115-5_115-3delTTT		splice_region_variant, intron_variant	Intron 1 of 3	ENST00000229135.4	NP_000610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNG	ENST00000229135.4	c.115-5_115-3delTTT		splice_region_variant, intron_variant	Intron 1 of 3	1	NM_000619.3	ENSP00000229135.3
IFNG-AS1	ENST00000536914.1	n.337-76267_337-76265delAAA		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147296 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00146 AC: 206 AN: 140762 Hom.: 0 AF XY: 0.00134 AC XY: 104 AN XY: 77408

Gnomad AFR exome AF: 0.00227

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00260

Gnomad EAS exome AF: 0.00111

Gnomad SAS exome AF: 0.00167

Gnomad FIN exome AF: 0.000916

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.000939

GnomAD4 exome AF: 0.000648 AC: 777 AN: 1199252 Hom.: 0 AF XY: 0.000673 AC XY: 402 AN XY: 597404

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.00129

Gnomad4 ASJ exome AF: 0.000819

Gnomad4 EAS exome AF: 0.000418

Gnomad4 SAS exome AF: 0.00180

Gnomad4 FIN exome AF: 0.000595

Gnomad4 NFE exome AF: 0.000552

Gnomad4 OTH exome AF: 0.000544

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147296 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71642

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs2234686; hg19: chr12-68552041;