12-68158714-AGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr12-68158714-A-AGTGTGTGT
• rs34079299
• NM_000619.3:c.115-463_115-456dupACACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000619.3(IFNG):​c.115-463_115-456dupACACACAC 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 0.010 (34 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1536/148784) while in subpopulation AFR AF = 0.0337 (1366/40528). AF 95% confidence interval is 0.0322. There are 34 homozygotes in GnomAd4. There are 761 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 Unknown,AR gene

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.115-463_115-456dupACACACAC		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_115-455insACACACAC		intron	N/A	ENSP00000229135.3
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-75815_337-75814insGTGTGTGT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1527 AN: 148680 Hom.: 34 Cov.: 0

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00257

Gnomad SAS AF: 0.000854

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000403

Gnomad OTH AF: 0.0132

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

GnomAD4 genome AF: 0.0103 AC: 1536 AN: 148784 Hom.: 34 Cov.: 0 AF XY: 0.0105 AC XY: 761 AN XY: 72576

African (AFR) AF: 0.0337 AC: 1366 AN: 40528

American (AMR) AF: 0.00656 AC: 98 AN: 14930

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

East Asian (EAS) AF: 0.00258 AC: 13 AN: 5048

South Asian (SAS) AF: 0.000856 AC: 4 AN: 4672

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

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000403 AC: 27 AN: 66932

Other (OTH) AF: 0.0130 AC: 27 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;