rs5029924

Variant names:

• chr6-137866361-C-T
• rs5029924
• ENST00000763056.1:n.610G>A

Variant summary

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

The ENST00000763056.1(WAKMAR2):​n.610G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,172 control chromosomes in the GnomAD database, including 2,586 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 0.12 (2586 hom., cov: 32)
• Consequence: WAKMAR2 ENST00000763056.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 24 publications found

Genes affected

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

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: Labcorp Genetics (formerly Invitae)
• hereditary pediatric Behçet-like disease

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

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

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 = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP3	XM_011536095.2	c.-321C>T		5_prime_UTR_variant	Exon 1 of 10		XP_011534397.1
TNFAIP3	XM_047419283.1	c.-627C>T		5_prime_UTR_variant	Exon 1 of 9		XP_047275239.1
WAKMAR2	NR_049793.1	n.894+222G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAKMAR2	ENST00000763056.1	n.610G>A		non_coding_transcript_exon_variant	Exon 2 of 2
WAKMAR2	ENST00000763058.1	n.675G>A		non_coding_transcript_exon_variant	Exon 1 of 1
WAKMAR2	ENST00000448942.5	n.63+1281G>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18403 AN: 152054 Hom.: 2570 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.121 AC: 18465 AN: 152172 Hom.: 2586 Cov.: 32 AF XY: 0.117 AC XY: 8721 AN XY: 74388

African (AFR) AF: 0.345 AC: 14320 AN: 41458

American (AMR) AF: 0.0731 AC: 1118 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3470

East Asian (EAS) AF: 0.0320 AC: 166 AN: 5180

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4822

European-Finnish (FIN) AF: 0.0166 AC: 176 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2122 AN: 68010

Other (OTH) AF: 0.115 AC: 243 AN: 2110

Alfa AF: 0.0945 Hom.: 235

Bravo AF: 0.135

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.3
DANN	Benign	0.78
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5029924; hg19: chr6-138187498;