rs2069718

Positions:

• chr12-68156382-A-G
• chr12-68156382-A-T

Variant summary

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

The NM_000619.3(IFNG):​c.367-895T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,020 control chromosomes in the GnomAD database, including 19,711 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 0.50 (19711 hom., cov: 32)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNG	NM_000619.3	c.367-895T>C		intron_variant		ENST00000229135.4	NP_000610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNG	ENST00000229135.4	c.367-895T>C		intron_variant		1	NM_000619.3	ENSP00000229135	P1
IFNG-AS1	ENST00000536914.1	n.337-78147A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75427 AN: 151902 Hom.: 19692 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.497 AC: 75488 AN: 152020 Hom.: 19711 Cov.: 32 AF XY: 0.485 AC XY: 36022 AN XY: 74284

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.532

Alfa AF: 0.580 Hom.: 35346

Bravo AF: 0.491

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.68

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: rs2069718; hg19: chr12-68550162;