12-68158261-TAAAAAAAA-TAAAAAAAAA

Variant names:

• chr12-68158261-T-TA
• rs2234686
• NM_000619.3:c.115-3dupT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000619.3(IFNG):​c.115-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0047 (0 hom.)
• Consequence: IFNG NM_000619.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNG	NM_000619.3	c.115-3dupT		splice_region_variant, intron_variant	Intron 1 of 3	ENST00000229135.4	NP_000610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNG	ENST00000229135.4	c.115-3_115-2insT		splice_region_variant, intron_variant	Intron 1 of 3	1	NM_000619.3	ENSP00000229135.3
IFNG-AS1	ENST00000536914.1	n.337-76268_337-76267insA		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 29 AN: 147314 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000202

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.000428

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000195

Gnomad OTH AF: 0.000495

GnomAD3 exomes AF: 0.00278 AC: 391 AN: 140762 Hom.: 0 AF XY: 0.00284 AC XY: 220 AN XY: 77408

Gnomad AFR exome AF: 0.000838

Gnomad AMR exome AF: 0.00358

Gnomad ASJ exome AF: 0.00260

Gnomad EAS exome AF: 0.00525

Gnomad SAS exome AF: 0.00187

Gnomad FIN exome AF: 0.00336

Gnomad NFE exome AF: 0.00260

Gnomad OTH exome AF: 0.00156

GnomAD4 exome AF: 0.00466 AC: 5597 AN: 1199862 Hom.: 0 Cov.: 0 AF XY: 0.00457 AC XY: 2735 AN XY: 597982

Gnomad4 AFR exome AF: 0.000979

Gnomad4 AMR exome AF: 0.00365

Gnomad4 ASJ exome AF: 0.00250

Gnomad4 EAS exome AF: 0.00469

Gnomad4 SAS exome AF: 0.00261

Gnomad4 FIN exome AF: 0.00356

Gnomad4 NFE exome AF: 0.00512

Gnomad4 OTH exome AF: 0.00352

GnomAD4 genome AF: 0.000197 AC: 29 AN: 147400 Hom.: 0 Cov.: 0 AF XY: 0.000251 AC XY: 18 AN XY: 71758

Gnomad4 AFR AF: 0.000124

Gnomad4 AMR AF: 0.000202

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.000428

Gnomad4 NFE AF: 0.000195

Gnomad4 OTH AF: 0.000490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2234686; hg19: chr12-68552041;