chr12-68157035-T-C

Variant names:

• chr12-68157035-T-C
• rs2069716
• NM_000619.3:c.366+878A>G

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+878A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 152,256 control chromosomes in the GnomAD database, including 152 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 0.037 (152 hom., cov: 32)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 24 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNG	NM_000619.3	MANE Select	c.366+878A>G		intron	N/A	NP_000610.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNG	ENST00000229135.4	TSL:1 MANE Select	c.366+878A>G		intron	N/A	ENSP00000229135.3
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-77494T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5689 AN: 152138 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0373 AC: 5684 AN: 152256 Hom.: 152 Cov.: 32 AF XY: 0.0350 AC XY: 2608 AN XY: 74434

African (AFR) AF: 0.00919 AC: 382 AN: 41546

American (AMR) AF: 0.0427 AC: 653 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4826

European-Finnish (FIN) AF: 0.0329 AC: 349 AN: 10608

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0580 AC: 3947 AN: 68010

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0527 Hom.: 141

Bravo AF: 0.0383

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.74
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

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: rs2069716; hg19: chr12-68550815;