rs3138557

Variant names:

• chr12-68158710-TGCGA-T
• rs3138557
• NM_000619.3:c.115-455_115-452delTCGC

Variant summary

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

The NM_000619.3(IFNG):​c.115-455_115-452delTCGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 26)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 19 publications found

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

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
IFNG	NM_000619.3	c.115-455_115-452delTCGC		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.115-455_115-452delTCGC		intron_variant	Intron 1 of 3	1	NM_000619.3	ENSP00000229135.3
IFNG-AS1	ENST00000536914.1	n.337-75818_337-75815delGCGA		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes Cov.: 26

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45

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

Other links and lift over

dbSNP: rs3138557; hg19: chr12-68552490;