12-68157629-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNG	NM_000619.3	c.366+284G>A		intron_variant		ENST00000229135.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNG	ENST00000229135.4	c.366+284G>A		intron_variant		1	NM_000619.3	P1
IFNG-AS1	ENST00000536914.1	n.337-76900C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.770

Alfa AF: 0.710 Hom.: 4812

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.0
Dann	Benign	0.56

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: rs1861494; hg19: chr12-68551409;