chr12-68157416-G-A

Variant names:

• chr12-68157416-G-A
• rs1861493
• NM_000619.3:c.366+497C>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.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
• Publications: 53 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=-0.89).
• 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 rank	MANE	Protein	UniProt
IFNG	NM_000619.3	c.366+497C>T		intron_variant	Intron 3 of 3	ENST00000229135.4	NP_000610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNG	ENST00000229135.4	c.366+497C>T		intron_variant	Intron 3 of 3	1	NM_000619.3	ENSP00000229135.3
IFNG-AS1	ENST00000536914.1	n.337-77113G>A		intron_variant	Intron 5 of 5	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

African (AFR) AF: 0.889 AC: 36905 AN: 41508

American (AMR) AF: 0.767 AC: 11710 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2737 AN: 3468

East Asian (EAS) AF: 0.669 AC: 3447 AN: 5156

South Asian (SAS) AF: 0.849 AC: 4087 AN: 4816

European-Finnish (FIN) AF: 0.595 AC: 6257 AN: 10524

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47901 AN: 67972

Other (OTH) AF: 0.785 AC: 1654 AN: 2108

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
PhyloP100		-1.0
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: rs1861493; hg19: chr12-68551196;