dbSNP rs2069718: IFNG:c.367-895T>C (chr12-68156382-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_000619.3(IFNG):c.367-895T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.497 (AC=75,488) in the gnomAD database across 152,020 control chromosomes, including 19,711 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.592. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 19711 hom., cov: 32)

Consequence

IFNG
NM_000619.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Publications

117 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 69
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

IFNG links:

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

IFNG-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000619.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5922 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000619.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNG	NM_000619.3	MANE Select	c.367-895T>C		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.367-895T>C		intron	N/A	ENSP00000229135.3	P01579
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-78147A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75427

AN:

151902

Hom.:

19692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.597

Gnomad OTH

AF:

0.527

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

GnomAD4 genome

AF:

0.497

AC:

75488

AN:

152020

Hom.:

19711

Cov.:

AF XY:

0.485

AC XY:

36022

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.407

AC:

16884

AN:

41456

American (AMR)

AF:

0.429

AC:

6552

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.598

AC:

2074

AN:

3470

East Asian (EAS)

AF:

0.156

AC:

809

AN:

5170

South Asian (SAS)

AF:

0.438

AC:

2112

AN:

4818

European-Finnish (FIN)

AF:

0.437

AC:

4611

AN:

10560

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.597

AC:

40571

AN:

67948

Other (OTH)

AF:

0.532

AC:

1124

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1885

3770

5655

7540

9425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.571

Hom.:

46251

Bravo

AF:

0.491

Asia WGS

AF:

0.386

AC:

1342

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.107

AC:

13108

AN:

122436

Turkish Variome

AF:

0.589

AC:

910

AN:

1546

Hom.:

272

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.139

AC:

1247

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.534

AC:

1251

AN:

2342

Hom.:

353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.9

(source)

DANN

Benign

0.68

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over