12-68158261-TAAAAAAAA-TAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000619.3(IFNG):​c.115-3delT 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. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (42118 hom., cov: 0)
  • Exomes 𝑓: 0.52 (47710 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFNG NM_000619.3 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 12-68158261-TA-T is Benign according to our data. Variant chr12-68158261-TA-T is described in ClinVar as Benign. ClinVar VariationId is 402962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

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.115-3delT		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.115-3delT		splice_region intron	N/A	ENSP00000229135.3	P01579
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-76267delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.754 AC: 111016 AN: 147200 Hom.: 42074 Cov.: 0

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.929

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.773

GnomAD2 exomes AF: 0.547 AC: 76931 AN: 140762 AF XY: 0.546

Gnomad AFR exome AF: 0.607

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.537

Gnomad FIN exome AF: 0.530

Gnomad NFE exome AF: 0.549

Gnomad OTH exome AF: 0.539

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.522 AC: 617998 AN: 1183798 Hom.: 47710 Cov.: 0 AF XY: 0.522 AC XY: 308028 AN XY: 589982

African (AFR) AF: 0.559 AC: 13693 AN: 24478

American (AMR) AF: 0.517 AC: 14316 AN: 27690

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 10733 AN: 20682

East Asian (EAS) AF: 0.505 AC: 16992 AN: 33672

South Asian (SAS) AF: 0.534 AC: 34187 AN: 63982

European-Finnish (FIN) AF: 0.500 AC: 21127 AN: 42282

Middle Eastern (MID) AF: 0.650 AC: 3048 AN: 4686

European-Non Finnish (NFE) AF: 0.521 AC: 478093 AN: 917244

Other (OTH) AF: 0.526 AC: 25809 AN: 49082

GnomAD4 genome AF: 0.754 AC: 111106 AN: 147288 Hom.: 42118 Cov.: 0 AF XY: 0.752 AC XY: 53894 AN XY: 71698

African (AFR) AF: 0.872 AC: 35042 AN: 40190

American (AMR) AF: 0.761 AC: 11286 AN: 14834

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2698 AN: 3424

East Asian (EAS) AF: 0.679 AC: 3428 AN: 5046

South Asian (SAS) AF: 0.837 AC: 3925 AN: 4688

European-Finnish (FIN) AF: 0.597 AC: 5563 AN: 9322

Middle Eastern (MID) AF: 0.940 AC: 265 AN: 282

European-Non Finnish (NFE) AF: 0.702 AC: 46723 AN: 66566

Other (OTH) AF: 0.777 AC: 1583 AN: 2038

Alfa AF: 0.565 Hom.: 1361

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 69 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2234686;

hg19: chr12-68552041;