rs5029964

Variant names:

• chr6-137876204-A-G
• rs5029964
• NM_001270508.2:c.805+38A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001270508.2(TNFAIP3):​c.805+38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,542,300 control chromosomes in the GnomAD database, including 5 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 0.0011 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 1 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: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hereditary pediatric Behçet-like disease

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287393 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00114 (173/152344) while in subpopulation AMR AF = 0.00425 (65/15300). AF 95% confidence interval is 0.00342. There are 2 homozygotes in GnomAd4. There are 92 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 173 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270508.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	NM_001270508.2	MANE Select	c.805+38A>G		intron	N/A	NP_001257437.1	P21580
	TNFAIP3	NM_001270507.2		c.805+38A>G		intron	N/A	NP_001257436.1	P21580
	TNFAIP3	NM_006290.4		c.805+38A>G		intron	N/A	NP_006281.1	P21580

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	ENST00000612899.5	TSL:5 MANE Select	c.805+38A>G		intron	N/A	ENSP00000481570.1	P21580
	TNFAIP3	ENST00000237289.8	TSL:1	c.805+38A>G		intron	N/A	ENSP00000237289.4	P21580
	TNFAIP3	ENST00000420009.6	TSL:3	c.805+38A>G		intron	N/A	ENSP00000401562.2	P21580

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 173 AN: 152226 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000662 AC: 150 AN: 226678 AF XY: 0.000699

Gnomad AFR exome AF: 0.000320

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.000739

GnomAD4 exome AF: 0.00123 AC: 1710 AN: 1389956 Hom.: 3 Cov.: 22 AF XY: 0.00120 AC XY: 829 AN XY: 693242

African (AFR) AF: 0.000256 AC: 8 AN: 31246

American (AMR) AF: 0.000896 AC: 34 AN: 37932

Ashkenazi Jewish (ASJ) AF: 0.0000408 AC: 1 AN: 24538

East Asian (EAS) AF: 0.00 AC: 0 AN: 39032

South Asian (SAS) AF: 0.00 AC: 0 AN: 79182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52774

Middle Eastern (MID) AF: 0.000720 AC: 4 AN: 5554

European-Non Finnish (NFE) AF: 0.00152 AC: 1610 AN: 1062004

Other (OTH) AF: 0.000919 AC: 53 AN: 57694

GnomAD4 genome AF: 0.00114 AC: 173 AN: 152344 Hom.: 2 Cov.: 33 AF XY: 0.00123 AC XY: 92 AN XY: 74508

African (AFR) AF: 0.000433 AC: 18 AN: 41578

American (AMR) AF: 0.00425 AC: 65 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00128 AC: 87 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000764 Hom.: 0

Bravo AF: 0.000884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.89
DANN	Benign	0.80
PhyloP100		-0.095

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: rs5029964; hg19: chr6-138197341;