6-137871624-A-G

Variant names:

• chr6-137871624-A-G
• rs719150
• NM_001270508.2:c.295+102A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001270508.2(TNFAIP3):​c.295+102A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,321,254 control chromosomes in the GnomAD database, including 12,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (5043 hom., cov: 32)
  • Exomes 𝑓: 0.094 (7499 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.792
• Publications: 16 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-137871624-A-G is Benign according to our data. Variant chr6-137871624-A-G is described in ClinVar as Benign. ClinVar VariationId is 1262636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.295+102A>G		intron_variant	Intron 2 of 8	ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.295+102A>G		intron_variant	Intron 2 of 8	5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29149 AN: 152032 Hom.: 5022 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0558

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.0938 AC: 109687 AN: 1169104 Hom.: 7499 AF XY: 0.0935 AC XY: 54477 AN XY: 582746

African (AFR) AF: 0.471 AC: 12515 AN: 26554

American (AMR) AF: 0.135 AC: 4000 AN: 29622

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 2365 AN: 19114

East Asian (EAS) AF: 0.0717 AC: 2726 AN: 38034

South Asian (SAS) AF: 0.102 AC: 6764 AN: 66224

European-Finnish (FIN) AF: 0.0277 AC: 1159 AN: 41878

Middle Eastern (MID) AF: 0.136 AC: 461 AN: 3400

European-Non Finnish (NFE) AF: 0.0825 AC: 73776 AN: 894138

Other (OTH) AF: 0.118 AC: 5921 AN: 50140

GnomAD4 genome AF: 0.192 AC: 29221 AN: 152150 Hom.: 5043 Cov.: 32 AF XY: 0.186 AC XY: 13850 AN XY: 74408

African (AFR) AF: 0.466 AC: 19298 AN: 41448

American (AMR) AF: 0.164 AC: 2515 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3470

East Asian (EAS) AF: 0.0561 AC: 291 AN: 5188

South Asian (SAS) AF: 0.0972 AC: 469 AN: 4824

European-Finnish (FIN) AF: 0.0253 AC: 269 AN: 10612

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0802 AC: 5455 AN: 67996

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.120 Hom.: 7608

Bravo AF: 0.212

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

not provided Benign:1

May 16, 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	-0.89
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs719150; hg19: chr6-138192761;