6-137874929-T-G

Position:

chr6-137874929-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001270508.2(TNFAIP3):c.380T>G(p.Phe127Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,614,106 control chromosomes in the GnomAD database, including 6,197 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2847 hom., cov: 32)

Exomes 𝑓: 0.043 ( 3350 hom. )

Consequence

TNFAIP3
NM_001270508.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 1.33

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011356473).

BP6

Variant 6-137874929-T-G is Benign according to our data. Variant chr6-137874929-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 135334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2 linkuse as main transcript	c.380T>G	p.Phe127Cys	missense_variant	3/9	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.380T>G	p.Phe127Cys	missense_variant	3/9	5	NM_001270508.2	ENSP00000481570	P1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19203

AN:

152110

Hom.:

2837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0732

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.0425

Gnomad SAS

AF:

0.0316

Gnomad FIN

AF:

0.0168

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0313

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.0542

AC:

13619

AN:

251476

Hom.:

1255

AF XY:

0.0480

AC XY:

6524

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.364

Gnomad AMR exome

AF:

0.0356

Gnomad ASJ exome

AF:

0.0516

Gnomad EAS exome

AF:

0.0370

Gnomad SAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.0329

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0425

AC:

62168

AN:

1461878

Hom.:

3350

Cov.:

AF XY:

0.0412

AC XY:

29941

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.367

Gnomad4 AMR exome

AF:

0.0395

Gnomad4 ASJ exome

AF:

0.0473

Gnomad4 EAS exome

AF:

0.0582

Gnomad4 SAS exome

AF:

0.0309

Gnomad4 FIN exome

AF:

0.0161

Gnomad4 NFE exome

AF:

0.0333

Gnomad4 OTH exome

AF:

0.0604

GnomAD4 genome

AF:

0.126

AC:

19251

AN:

152228

Hom.:

2847

Cov.:

AF XY:

0.123

AC XY:

9121

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.363

Gnomad4 AMR

AF:

0.0731

Gnomad4 ASJ

AF:

0.0441

Gnomad4 EAS

AF:

0.0430

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.0168

Gnomad4 NFE

AF:

0.0313

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.0505

Hom.:

1403

Bravo

AF:

0.140

TwinsUK

AF:

0.0348

AC:

129

ALSPAC

AF:

0.0332

AC:

128

ESP6500AA

AF:

0.356

AC:

1570

ESP6500EA

AF:

0.0321

AC:

276

ExAC

AF:

0.0613

AC:

7438

Asia WGS

AF:

0.0510

AC:

180

AN:

3478

EpiCase

AF:

0.0346

EpiControl

AF:

0.0346

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 30, 2019	This variant is associated with the following publications: (PMID: 31131138, 30529365, 26338037, 26502338, 19165918, 24023622, 24728327, 20169177, 19838193, 19165919, 19774492, 20617138, 20483768, 22924496, 21326317, 24159176, 20112363, 23261300) -

Autoinflammatory syndrome, familial, Behcet-like 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.39

T;T;T;.;T;T;T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

T;T;.;T;T;T;T;T

MetaRNN

Benign

0.0011

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;L;.;.;.;.;.

MutationTaster

Benign

0.14

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.9

.;D;D;.;.;.;.;.

REVEL

Benign

0.022

Sift

Benign

0.22

.;T;T;.;.;.;.;.

Sift4G

Benign

0.11

T;T;T;T;T;T;T;T

Polyphen

0.0080

B;.;B;.;.;.;.;.

Vest4

0.14

MPC

0.49

ClinPred

0.039

GERP RS

-0.057

Varity_R

0.46

gMVP

0.55

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

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