chr12-68158714-AGTGT-A

Position:

• chr12-68158714-AGTGT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000619.3(IFNG):​c.115-459_115-456delACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.021 (100 hom., cov: 0)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: risk factor no assertion criteria provided O:2
• Conservation: PhyloP100: 0.144

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:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNG	NM_000619.3	c.115-459_115-456delACAC		intron_variant		ENST00000229135.4	NP_000610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNG	ENST00000229135.4	c.115-459_115-456delACAC		intron_variant		1	NM_000619.3	ENSP00000229135.3
IFNG-AS1	ENST00000536914.1	n.337-75789_337-75786delTGTG		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3177 AN: 148620 Hom.: 99 Cov.: 0

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00872

Gnomad ASJ AF: 0.00233

Gnomad EAS AF: 0.000989

Gnomad SAS AF: 0.00171

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00167

Gnomad OTH AF: 0.0190

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

GnomAD4 genome AF: 0.0214 AC: 3186 AN: 148724 Hom.: 100 Cov.: 0 AF XY: 0.0222 AC XY: 1613 AN XY: 72528

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.00877

Gnomad4 ASJ AF: 0.00233

Gnomad4 EAS AF: 0.000991

Gnomad4 SAS AF: 0.00171

Gnomad4 FIN AF: 0.0393

Gnomad4 NFE AF: 0.00167

Gnomad4 OTH AF: 0.0188

ClinVar

Significance: risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

Submissions by phenotype

Tsc2 angiomyolipomas, renal, modifier of Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 01, 2004

- -

Aplastic anemia, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

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: rs34079299; hg19: chr12-68552494;