6-137878280-G-T

Position:

• chr6-137878280-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001270508.2(TNFAIP3):​c.987-152G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 658,668 control chromosomes in the GnomAD database, including 146,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27961 hom., cov: 33)
  • Exomes 𝑓: 0.68 (118448 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.456

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-137878280-G-T is Benign according to our data. Variant chr6-137878280-G-T is described in ClinVar as [Benign]. Clinvar id is 1275669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP3	NM_001270508.2	c.987-152G>T		intron_variant		ENST00000612899.5	NP_001257437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.987-152G>T		intron_variant		5	NM_001270508.2	ENSP00000481570.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89310 AN: 152008 Hom.: 27957 Cov.: 33

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.677 AC: 343131 AN: 506542 Hom.: 118448 AF XY: 0.679 AC XY: 178719 AN XY: 263070

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.593

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.921

Gnomad4 SAS exome AF: 0.690

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.587 AC: 89340 AN: 152126 Hom.: 27961 Cov.: 33 AF XY: 0.590 AC XY: 43867 AN XY: 74356

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.608

Alfa AF: 0.666 Hom.: 73691

Bravo AF: 0.573

Asia WGS AF: 0.714 AC: 2482 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.44
DANN	Benign	0.59

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: rs610604; hg19: chr6-138199417;