rs1861493

chr12-68157416-G-Achr12-68157416-G-Cchr12-68157416-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000619.3(IFNG):c.366+497C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,034 control chromosomes in the GnomAD database, including 44,711 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 0.76 (44711 hom., cov: 30)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNG	NM_000619.3	c.366+497C>T		intron_variant		ENST00000229135.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNG	ENST00000229135.4	c.366+497C>T		intron_variant		1	NM_000619.3	P1
IFNG-AS1	ENST00000536914.1	n.337-77113G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115447 AN: 151916 Hom.: 44645 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.760 AC: 115574 AN: 152034 Hom.: 44711 Cov.: 30 AF XY: 0.757 AC XY: 56239 AN XY: 74282

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.785

Alfa AF: 0.654 Hom.: 2448

Bravo AF: 0.776

Asia WGS AF: 0.799 AC: 2780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.12
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1861493; hg19: chr12-68551196;