chr12-68158714-A-AGTGTGT

Position:

• chr12-68158714-A-AGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000619.3(IFNG):​c.115-456_115-455insACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.014 (28 hom., cov: 0)
• Consequence: IFNG NM_000619.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2085/148790) while in subpopulation AFR AF= 0.0428 (1734/40536). AF 95% confidence interval is 0.0411. There are 28 homozygotes in gnomad4. There are 1017 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNG	NM_000619.3	c.115-456_115-455insACACAC		intron_variant		ENST00000229135.4	NP_000610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNG	ENST00000229135.4	c.115-456_115-455insACACAC		intron_variant		1	NM_000619.3	ENSP00000229135	P1
IFNG-AS1	ENST00000536914.1	n.337-75791_337-75786dup		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2083 AN: 148686 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00664

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.00406

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.0117

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

GnomAD4 genome AF: 0.0140 AC: 2085 AN: 148790 Hom.: 28 Cov.: 0 AF XY: 0.0140 AC XY: 1017 AN XY: 72570

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.00656

Gnomad4 ASJ AF: 0.0116

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.00407

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000971

Gnomad4 OTH AF: 0.0116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;