rs2234686

Variant names:

• chr12-68158261-TAAAAAAAA-T
• rs2234686
• NM_000619.3:c.115-10_115-3delTTTTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr12-68158261-TAAAAAAAA-T
• chr12-68158261-TAAAAAAAA-TAAAA
• chr12-68158261-TAAAAAAAA-TAAAAA
• chr12-68158261-TAAAAAAAA-TAAAAAA
• chr12-68158261-TAAAAAAAA-TAAAAAAA
• chr12-68158261-TAAAAAAAA-TAAAAAAAAA
• chr12-68158261-TAAAAAAAA-TAAAAAAAAAA
• chr12-68158261-TAAAAAAAA-TAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000619.3(IFNG):​c.115-10_115-3delTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000828 in 1,208,144 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: IFNG NM_000619.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.115-10_115-3delTTTTTTTT		splice_region intron	N/A	NP_000610.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNG	ENST00000229135.4	TSL:1 MANE Select	c.115-10_115-3delTTTTTTTT		splice_region intron	N/A	ENSP00000229135.3
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-76267_337-76260delAAAAAAAA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.28e-7 AC: 1 AN: 1208144 Hom.: 0 AF XY: 0.00000166 AC XY: 1 AN XY: 602032

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

African (AFR) AF: 0.00 AC: 0 AN: 24580

American (AMR) AF: 0.00 AC: 0 AN: 28086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20930

East Asian (EAS) AF: 0.00 AC: 0 AN: 36048

South Asian (SAS) AF: 0.00 AC: 0 AN: 64332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 935564

Other (OTH) AF: 0.0000200 AC: 1 AN: 49980

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2234686; hg19: chr12-68552041;