6-137871624-A-G

Variant names:

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

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 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

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

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

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;