Variant 6-137875680-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001270508.2(TNFAIP3):c.487-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,613,456 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 57 hom. )

Consequence

TNFAIP3
NM_001270508.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.002719

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.378

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-137875680-C-G is Benign according to our data. Variant chr6-137875680-C-G is described in ClinVar as [Benign]. Clinvar id is 769695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (2254/152176) while in subpopulation AFR AF= 0.0459 (1906/41496). AF 95% confidence interval is 0.0442. There are 38 homozygotes in gnomad4. There are 1056 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2254 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2 linkuse as main transcript	c.487-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5 linkuse as main transcript	c.487-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001270508.2	ENSP00000481570	P1

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2249

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00149

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00511

AC:

1282

AN:

250862

Hom.:

AF XY:

0.00402

AC XY:

545

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.0479

Gnomad AMR exome

AF:

0.00766

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00159

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00293

AC:

4275

AN:

1461280

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1978

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0476

Gnomad4 AMR exome

AF:

0.00886

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00157

Gnomad4 OTH exome

AF:

0.00721

GnomAD4 genome

AF:

0.0148

AC:

2254

AN:

152176

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1056

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0459

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00149

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00534

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00235

EpiControl

AF:

0.00237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Autoinflammatory syndrome, familial, Behcet-like 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Apr 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.4

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0027

dbscSNV1_RF

Benign

0.058

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.

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