12-68158714-AGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr12-68158714-A-AGTGTGT
• rs34079299
• NM_000619.3:c.115-461_115-456dupACACAC

Variant summary

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

The NM_000619.3(IFNG):​c.115-461_115-456dupACACAC 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 0.014 (28 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 = 0.014 (2085/148790) while in subpopulation AFR AF = 0.0428 (1734/40536). AF 95% confidence interval is 0.0411. There are 28 homozygotes in GnomAd4. There are 1017 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 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.115-461_115-456dupACACAC		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_115-455insACACAC		intron	N/A	ENSP00000229135.3
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-75815_337-75814insGTGTGT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2083 AN: 148686 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00664

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.00406

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.0117

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

GnomAD4 genome AF: 0.0140 AC: 2085 AN: 148790 Hom.: 28 Cov.: 0 AF XY: 0.0140 AC XY: 1017 AN XY: 72570

African (AFR) AF: 0.0428 AC: 1734 AN: 40536

American (AMR) AF: 0.00656 AC: 98 AN: 14932

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 40 AN: 3438

East Asian (EAS) AF: 0.0206 AC: 104 AN: 5048

South Asian (SAS) AF: 0.00407 AC: 19 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: 0.000971 AC: 65 AN: 66928

Other (OTH) AF: 0.0116 AC: 24 AN: 2072

Alfa AF: 0.000440 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;