rs121913164

Variant names:

• chr12-68157774-A-G
• rs121913164
• NM_000619.3:c.366+139T>C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_000619.3(IFNG):​c.366+139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000688 in 607,810 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.398

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAd4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNG	NM_000619.3	c.366+139T>C		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+139T>C		intron_variant	Intron 3 of 3	1	NM_000619.3	ENSP00000229135.3
IFNG-AS1	ENST00000536914.1	n.337-76755A>G		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 295 AN: 152220 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00687

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.000268 AC: 122 AN: 455472 Hom.: 0 AF XY: 0.000206 AC XY: 49 AN XY: 238024

Gnomad4 AFR exome AF: 0.00831

Gnomad4 AMR exome AF: 0.000203

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000650

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000350

Gnomad4 OTH exome AF: 0.000435

GnomAD4 genome AF: 0.00194 AC: 296 AN: 152338 Hom.: 2 Cov.: 32 AF XY: 0.00189 AC XY: 141 AN XY: 74502

Gnomad4 AFR AF: 0.00688

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.00218

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

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Human Evolutionary Genetics, Institut Pasteur

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.64
DANN	Benign	0.34

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: rs121913164; hg19: chr12-68551554;