12-68158714-AGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr12-68158714-A-AGTGTGTGTGT
• rs34079299
• NM_000619.3:c.115-465_115-456dupACACACACAC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1 BS2_Supporting

The NM_000619.3(IFNG):​c.115-465_115-456dupACACACACAC 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 0.0017 (5 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: Likely_benign. The variant received -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00171 (254/148800) while in subpopulation EAS AF = 0.0365 (184/5044). AF 95% confidence interval is 0.0322. There are 5 homozygotes in GnomAd4. There are 142 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 Unknown,AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.115-465_115-456dupACACACACAC		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_115-455insACACACACAC		intron	N/A	ENSP00000229135.3
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-75815_337-75814insGTGTGTGTGT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 254 AN: 148696 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.00278

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000105

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00171 AC: 254 AN: 148800 Hom.: 5 Cov.: 0 AF XY: 0.00196 AC XY: 142 AN XY: 72578

African (AFR) AF: 0.00113 AC: 46 AN: 40544

American (AMR) AF: 0.000268 AC: 4 AN: 14934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.0365 AC: 184 AN: 5044

South Asian (SAS) AF: 0.00278 AC: 13 AN: 4672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000105 AC: 7 AN: 66932

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 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

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;