dbSNP rs5029964: TNFAIP3:c.805+38A>G (chr6-137876204-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001270508.2(TNFAIP3):c.805+38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,542,300 control chromosomes in the GnomAD database, including 5 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 0.0011 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

TNFAIP3
NM_001270508.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0950

Publications

1 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 Gene-Disease associations (from GenCC):

autoinflammatory syndrome, familial, Behcet-like 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hereditary pediatric Behçet-like disease
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

TNFAIP3 links:

ENSG00000287393 (HGNC:):

ENSG00000287393 links:

Genome browser will be placed here

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=-0.83).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00114 (173/152344) while in subpopulation AMR AF = 0.00425 (65/15300). AF 95% confidence interval is 0.00342. There are 2 homozygotes in GnomAd4. There are 92 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 173 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2 link	c.805+38A>G		intron_variant	Intron 5 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.805+38A>G		intron_variant	Intron 5 of 8	5	NM_001270508.2	ENSP00000481570.1		P21580

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

173

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000662

AC:

150

AN:

226678

AF XY:

0.000699

show subpopulations

Gnomad AFR exome

AF:

0.000320

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000739

GnomAD4 exome

AF:

0.00123

AC:

1710

AN:

1389956

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

829

AN XY:

693242

show subpopulations

African (AFR)

AF:

0.000256

AC:

AN:

31246

American (AMR)

AF:

0.000896

AC:

AN:

37932

Ashkenazi Jewish (ASJ)

AF:

0.0000408

AC:

AN:

24538

East Asian (EAS)

AF:

0.00

AC:

AN:

39032

South Asian (SAS)

AF:

0.00

AC:

AN:

79182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52774

Middle Eastern (MID)

AF:

0.000720

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.00152

AC:

1610

AN:

1062004

Other (OTH)

AF:

0.000919

AC:

AN:

57694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

168

253

337

421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.00114

AC:

173

AN:

152344

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41578

American (AMR)

AF:

0.00425

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00128

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000764

Hom.:

Bravo

AF:

0.000884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.89

(source)

DANN

Benign

0.80

PhyloP100

-0.095

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