Genetic Variant IFNG:c.115-3delT (chr12-68158261-TA-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.416

Variant links:

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 links:

IFNG-AS1 (HGNC:43910): (IFNG antisense RNA 1)

IFNG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 402962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-68158261-TA-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNG	NM_000619.3 link	c.115-3delT		splice_region_variant, intron_variant	Intron 1 of 3	ENST00000229135.4	NP_000610.2	P01579A0A7R8GUN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNG	ENST00000229135.4 link	c.115-3delT		splice_region_variant, intron_variant	Intron 1 of 3	1	NM_000619.3	ENSP00000229135.3		P01579
IFNG-AS1	ENST00000536914.1 link	n.337-76267delA		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.754

AC:

111016

AN:

147200

Hom.:

42074

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.547

AC:

76931

AN:

140762

Hom.:

7916

AF XY:

0.546

AC XY:

42230

AN XY:

77408

show subpopulations

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 SAS exome

AF:

0.543

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.:

AF XY:

0.522

AC XY:

308028

AN XY:

589982

show subpopulations

Gnomad4 AFR exome

AF:

0.559

Gnomad4 AMR exome

AF:

0.517

Gnomad4 ASJ exome

AF:

0.519

Gnomad4 EAS exome

AF:

0.505

Gnomad4 SAS exome

AF:

0.534

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.521

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.754

AC:

111106

AN:

147288

Hom.:

42118

Cov.:

AF XY:

0.752

AC XY:

53894

AN XY:

71698

show subpopulations

Gnomad4 AFR

AF:

0.872

Gnomad4 AMR

AF:

0.761

Gnomad4 ASJ

AF:

0.788

Gnomad4 EAS

AF:

0.679

Gnomad4 SAS

AF:

0.837

Gnomad4 FIN

AF:

0.597

Gnomad4 NFE

AF:

0.702

Gnomad4 OTH

AF:

0.777

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Immunodeficiency 69

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

12-68158261-TAAAAAAAA-TAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over