Genetic Variant IFNG:c.115-4_115-3delTT (chr12-68158261-TAA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000619.3(IFNG):c.115-4_115-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,210,686 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.10 ( 0 hom. )

Consequence

IFNG
NM_000619.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-68158261-TAA-T is Benign according to our data. Variant chr12-68158261-TAA-T is described in ClinVar as [Benign]. Clinvar id is 1282751.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNG	NM_000619.3 link	c.115-4_115-3delTT		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.115-4_115-3delTT		splice_region_variant, intron_variant	Intron 1 of 3	1	NM_000619.3	ENSP00000229135.3		P01579
IFNG-AS1	ENST00000536914.1 link	n.337-76267_337-76266delAA		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

194

AN:

147022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00155

Gnomad ASJ

AF:

0.000292

Gnomad EAS

AF:

0.000790

Gnomad SAS

AF:

0.000425

Gnomad FIN

AF:

0.00624

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00111

Gnomad OTH

AF:

0.00198

GnomAD3 exomes

AF:

0.152

AC:

21421

AN:

140762

Hom.:

AF XY:

0.157

AC XY:

12143

AN XY:

77408

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.238

Gnomad FIN exome

AF:

0.0911

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.104

AC:

110518

AN:

1063588

Hom.:

AF XY:

0.107

AC XY:

56624

AN XY:

528492

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.0727

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.0849

Gnomad4 NFE exome

AF:

0.0956

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.00132

AC:

194

AN:

147098

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

106

AN XY:

71592

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00155

Gnomad4 ASJ

AF:

0.000292

Gnomad4 EAS

AF:

0.000791

Gnomad4 SAS

AF:

0.000426

Gnomad4 FIN

AF:

0.00624

Gnomad4 NFE

AF:

0.00111

Gnomad4 OTH

AF:

0.00196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 09, 2021

GeneDx

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)

0.020

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-TAAAAAA

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