rs5029926

Variant names:

• chr6-137868378-A-G
• rs5029926
• NM_001270508.2:c.-16+836A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-137868378-A-G
• chr6-137868378-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270508.2(TNFAIP3):​c.-16+836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,198 control chromosomes in the GnomAD database, including 5,022 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 0.19 (5022 hom., cov: 32)
  • Exomes 𝑓: 0.074 (0 hom.)
• Consequence: TNFAIP3 NM_001270508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 11 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]

WAKMAR2 (HGNC:53754): (wound and keratinocyte migration associated lncRNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	NM_001270508.2	MANE Select	c.-16+836A>G		intron	N/A	NP_001257437.1
	TNFAIP3	NM_001270507.2		c.-16+860A>G		intron	N/A	NP_001257436.1
	TNFAIP3	NM_006290.4		c.-16+884A>G		intron	N/A	NP_006281.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP3	ENST00000612899.5	TSL:5 MANE Select	c.-16+836A>G		intron	N/A	ENSP00000481570.1
	TNFAIP3	ENST00000237289.8	TSL:1	c.-16+884A>G		intron	N/A	ENSP00000237289.4
	TNFAIP3	ENST00000420009.6	TSL:3	c.-16+860A>G		intron	N/A	ENSP00000401562.2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29067 AN: 151932 Hom.: 5003 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.0743 AC: 11 AN: 148 Hom.: 0 AF XY: 0.0476 AC XY: 4 AN XY: 84

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0809 AC: 11 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.192 AC: 29130 AN: 152050 Hom.: 5022 Cov.: 32 AF XY: 0.186 AC XY: 13822 AN XY: 74350

African (AFR) AF: 0.465 AC: 19262 AN: 41422

American (AMR) AF: 0.162 AC: 2478 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3472

East Asian (EAS) AF: 0.0555 AC: 287 AN: 5172

South Asian (SAS) AF: 0.0971 AC: 468 AN: 4818

European-Finnish (FIN) AF: 0.0253 AC: 268 AN: 10600

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5456 AN: 67978

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.164 Hom.: 903

Bravo AF: 0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.73
DANN	Benign	0.55
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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: rs5029926; hg19: chr6-138189515; COSMIC: COSV52797655; COSMIC: COSV52797655;