12-68158714-AGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGT

Variant names:

• chr12-68158714-AGT-A
• rs34079299
• NM_000619.3:c.115-457_115-456delAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000619.3(IFNG):​c.115-457_115-456delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (10805 hom., cov: 0)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNG	NM_000619.3	c.115-457_115-456delAC		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.115-457_115-456delAC		intron_variant	Intron 1 of 3	1	NM_000619.3	ENSP00000229135.3
IFNG-AS1	ENST00000536914.1	n.337-75814_337-75813delGT		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.377 AC: 55882 AN: 148412 Hom.: 10791 Cov.: 0

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.377 AC: 55925 AN: 148514 Hom.: 10805 Cov.: 0 AF XY: 0.370 AC XY: 26812 AN XY: 72434

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34079299; hg19: chr12-68552494;