12-68158714-AGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000619.3(IFNG):​c.115-457_115-456dupAC 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 0.057 (253 hom., cov: 0)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 0 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNG	NM_000619.3	MANE Select	c.115-457_115-456dupAC		intron	N/A	NP_000610.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNG	ENST00000229135.4	TSL:1 MANE Select	c.115-456_115-455insAC		intron	N/A	ENSP00000229135.3
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-75815_337-75814insGT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8453 AN: 148646 Hom.: 253 Cov.: 0

Gnomad AFR AF: 0.0599

Gnomad AMI AF: 0.0320

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00929

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0568 AC: 8451 AN: 148750 Hom.: 253 Cov.: 0 AF XY: 0.0562 AC XY: 4080 AN XY: 72542

African (AFR) AF: 0.0598 AC: 2422 AN: 40520

American (AMR) AF: 0.0652 AC: 973 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 378 AN: 3438

East Asian (EAS) AF: 0.00931 AC: 47 AN: 5046

South Asian (SAS) AF: 0.0544 AC: 254 AN: 4668

European-Finnish (FIN) AF: 0.0461 AC: 459 AN: 9962

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0555 AC: 3716 AN: 66920

Other (OTH) AF: 0.0667 AC: 138 AN: 2068

Alfa AF: 0.0335 Hom.: 431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs34079299; hg19: chr12-68552494;