Genetic Variant NM_001270508.2:c.805+28A>C (chr6-137876194-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001270508.2(TNFAIP3):c.805+28A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 1,583,506 control chromosomes in the GnomAD database, including 319,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 23620 hom., cov: 32)

Exomes 𝑓: 0.64 ( 295461 hom. )

Consequence

TNFAIP3
NM_001270508.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.50

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 (BayesDel_noAF=-0.91).

BP6

Variant 6-137876194-A-C is Benign according to our data. Variant chr6-137876194-A-C is described in ClinVar as [Benign]. Clinvar id is 1281403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2 link	c.805+28A>C		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+28A>C		intron_variant	Intron 5 of 8	5	NM_001270508.2	ENSP00000481570.1		P21580

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78072

AN:

152004

Hom.:

23623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.647

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.647

Gnomad OTH

AF:

0.550

GnomAD3 exomes

AF:

0.620

AC:

148964

AN:

240196

Hom.:

48370

AF XY:

0.631

AC XY:

81907

AN XY:

129860

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.577

Gnomad ASJ exome

AF:

0.592

Gnomad EAS exome

AF:

0.856

Gnomad SAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.647

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

AF:

0.637

AC:

911558

AN:

1431386

Hom.:

295461

Cov.:

AF XY:

0.639

AC XY:

455444

AN XY:

712590

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.574

Gnomad4 ASJ exome

AF:

0.584

Gnomad4 EAS exome

AF:

0.859

Gnomad4 SAS exome

AF:

0.661

Gnomad4 FIN exome

AF:

0.640

Gnomad4 NFE exome

AF:

0.646

Gnomad4 OTH exome

AF:

0.615

GnomAD4 genome

AF:

0.513

AC:

78071

AN:

152120

Hom.:

23620

Cov.:

AF XY:

0.518

AC XY:

38547

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.561

Gnomad4 ASJ

AF:

0.571

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.664

Gnomad4 FIN

AF:

0.647

Gnomad4 NFE

AF:

0.647

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.625

Hom.:

29474

Bravo

AF:

0.494

Asia WGS

AF:

0.673

AC:

2339

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 79% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Autoinflammatory syndrome, familial, Behcet-like

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.30

DANN

Benign

0.42

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