NM_000619.3:c.366+284G>A

Variant names:

• chr12-68157629-C-T
• rs1861494
• NM_000619.3:c.366+284G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000619.3(IFNG):​c.366+284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,088 control chromosomes in the GnomAD database, including 42,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.75 (42856 hom., cov: 32)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.162
• Publications: 93 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-68157629-C-T is Benign according to our data. Variant chr12-68157629-C-T is described in ClinVar as Benign. ClinVar VariationId is 1259250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.836 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+284G>A		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+284G>A		intron	N/A	ENSP00000229135.3
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-76900C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113285 AN: 151970 Hom.: 42790 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.746 AC: 113412 AN: 152088 Hom.: 42856 Cov.: 32 AF XY: 0.743 AC XY: 55246 AN XY: 74316

African (AFR) AF: 0.843 AC: 35011 AN: 41520

American (AMR) AF: 0.755 AC: 11546 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2692 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3464 AN: 5168

South Asian (SAS) AF: 0.848 AC: 4088 AN: 4822

European-Finnish (FIN) AF: 0.596 AC: 6271 AN: 10528

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47842 AN: 67978

Other (OTH) AF: 0.770 AC: 1627 AN: 2114

Alfa AF: 0.702 Hom.: 9265

Bravo AF: 0.759

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		-0.16
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: rs1861494; hg19: chr12-68551409;