rs598493

chr6-137874265-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270508.2(TNFAIP3):c.296-580T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,064 control chromosomes in the GnomAD database, including 38,496 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (38496 hom., cov: 32)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFAIP3	NM_001270508.2	c.296-580T>C		intron_variant		ENST00000612899.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP3	ENST00000612899.5	c.296-580T>C		intron_variant		5	NM_001270508.2	P1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107778 AN: 151946 Hom.: 38464 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.728

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.709 AC: 107860 AN: 152064 Hom.: 38496 Cov.: 32 AF XY: 0.708 AC XY: 52656 AN XY: 74336

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.730

Alfa AF: 0.707 Hom.: 7582

Bravo AF: 0.711

Asia WGS AF: 0.811 AC: 2819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.4
Dann	Benign	0.33

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: rs598493; hg19: chr6-138195402;