12-68158261-TAAAAAAAA-TAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 9 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNG	NM_000619.3	MANE Select	c.115-3dupT		splice_region intron	N/A	NP_000610.2	P01579

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNG	ENST00000229135.4	TSL:1 MANE Select	c.115-3_115-2insT		splice_region intron	N/A	ENSP00000229135.3	P01579
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-76268_337-76267insA		intron	N/A

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

GnomAD2 exomes AF: 0.00278 AC: 391 AN: 140762 AF XY: 0.00284

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000979 AC: 24 AN: 24508

American (AMR) AF: 0.00365 AC: 102 AN: 27976

Ashkenazi Jewish (ASJ) AF: 0.00250 AC: 52 AN: 20838

East Asian (EAS) AF: 0.00469 AC: 167 AN: 35618

South Asian (SAS) AF: 0.00261 AC: 167 AN: 64086

European-Finnish (FIN) AF: 0.00356 AC: 155 AN: 43542

Middle Eastern (MID) AF: 0.000427 AC: 2 AN: 4686

European-Non Finnish (NFE) AF: 0.00512 AC: 4753 AN: 928928

Other (OTH) AF: 0.00352 AC: 175 AN: 49680

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.000124 AC: 5 AN: 40204

American (AMR) AF: 0.000202 AC: 3 AN: 14844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5054

South Asian (SAS) AF: 0.000426 AC: 2 AN: 4690

European-Finnish (FIN) AF: 0.000428 AC: 4 AN: 9338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000195 AC: 13 AN: 66622

Other (OTH) AF: 0.000490 AC: 1 AN: 2042

Alfa AF: 0.00 Hom.: 1361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42

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

Other links and lift over

dbSNP: rs2234686; hg19: chr12-68552041;