Genetic Variant TNFAIP3:c.-16+836A>G (chr6-137868378-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001270508.2(TNFAIP3):c.-16+836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,198 control chromosomes in the GnomAD database, including 5,022 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 5022 hom., cov: 32)

Exomes 𝑓: 0.074 ( 0 hom. )

Consequence

TNFAIP3
NM_001270508.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.867

Publications

11 publications found

Variant links:

Genes affected

TNFAIP3 (HGNC:11896): (TNF alpha induced protein 3) This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein and ubiqitin-editing enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The encoded protein, which has both ubiquitin ligase and deubiquitinase activities, is involved in the cytokine-mediated immune and inflammatory responses. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2012]

TNFAIP3 links:

WAKMAR2 (HGNC:53754): (wound and keratinocyte migration associated lncRNA 2)

WAKMAR2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2 link	c.-16+836A>G		intron_variant	Intron 1 of 8	ENST00000612899.5	NP_001257437.1	P21580

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5 link	c.-16+836A>G		intron_variant	Intron 1 of 8	5	NM_001270508.2	ENSP00000481570.1		P21580

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29067

AN:

151932

Hom.:

5003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.465

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0552

Gnomad SAS

AF:

0.0979

Gnomad FIN

AF:

0.0253

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0803

Gnomad OTH

AF:

0.173

GnomAD4 exome

AF:

0.0743

AC:

AN:

148

Hom.:

AF XY:

0.0476

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0809

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.192

AC:

29130

AN:

152050

Hom.:

5022

Cov.:

AF XY:

0.186

AC XY:

13822

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.465

AC:

19262

AN:

41422

American (AMR)

AF:

0.162

AC:

2478

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

425

AN:

3472

East Asian (EAS)

AF:

0.0555

AC:

287

AN:

5172

South Asian (SAS)

AF:

0.0971

AC:

468

AN:

4818

European-Finnish (FIN)

AF:

0.0253

AC:

268

AN:

10600

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0803

AC:

5456

AN:

67978

Other (OTH)

AF:

0.173

AC:

365

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

974

1948

2922

3896

4870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.164

Hom.:

903

Bravo

AF:

0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.73

(source)

DANN

Benign

0.55

PhyloP100

-0.87

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over