rs2430561

Positions:

• chr12-68158742-T-A
• chr12-68158742-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNG	NM_000619.3	c.115-483A>T		intron_variant		ENST00000229135.4	NP_000610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNG	ENST00000229135.4	c.115-483A>T		intron_variant		1	NM_000619.3	ENSP00000229135	P1
IFNG-AS1	ENST00000536914.1	n.337-75787T>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.402

Alfa AF: 0.400 Hom.: 1552

Bravo AF: 0.352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.78
DANN	Benign	0.48

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: rs2430561; hg19: chr12-68552522;