rs719150

Positions:

• chr6-137871624-A-G
• chr6-137871624-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.295+102A>G		intron_variant		ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.295+102A>G		intron_variant		5	NM_001270508.2	ENSP00000481570	P1

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

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.0717

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0277

Gnomad4 NFE exome AF: 0.0825

Gnomad4 OTH exome AF: 0.118

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

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0561

Gnomad4 SAS AF: 0.0972

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.0802

Gnomad4 OTH AF: 0.179

Alfa AF: 0.106 Hom.: 2294

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs719150; hg19: chr6-138192761;