NM_000619.3:c.115-483A>T

Variant names:

• chr12-68158742-T-A
• rs2430561
• NM_000619.3:c.115-483A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000619.3(IFNG):​c.115-483A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,380 control chromosomes in the GnomAD database, including 10,853 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10853 hom., cov: 31)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 733 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 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.115-483A>T		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.115-483A>T		intron	N/A	ENSP00000229135.3
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-75787T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54832 AN: 151266 Hom.: 10846 Cov.: 31

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.362 AC: 54844 AN: 151380 Hom.: 10853 Cov.: 31 AF XY: 0.355 AC XY: 26270 AN XY: 73932

African (AFR) AF: 0.226 AC: 9317 AN: 41162

American (AMR) AF: 0.325 AC: 4941 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1529 AN: 3460

East Asian (EAS) AF: 0.154 AC: 795 AN: 5164

South Asian (SAS) AF: 0.386 AC: 1852 AN: 4796

European-Finnish (FIN) AF: 0.338 AC: 3540 AN: 10480

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31420 AN: 67794

Other (OTH) AF: 0.402 AC: 845 AN: 2104

Alfa AF: 0.400 Hom.: 1552

Bravo AF: 0.352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.78
DANN	Benign	0.48
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2430561; hg19: chr12-68552522;