2-151364578-G-A

Variant names:

• chr2-151364578-G-A
• rs3755480
• NM_007115.4:c.232+498G>A

Variant summary

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

The NM_007115.4(TNFAIP6):​c.232+498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,104 control chromosomes in the GnomAD database, including 2,827 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 0.18 (2827 hom., cov: 32)
• Consequence: TNFAIP6 NM_007115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 3 publications found

Genes affected

TNFAIP6 (HGNC:11898): (TNF alpha induced protein 6) The protein encoded by this gene is a secretory protein that contains a hyaluronan-binding domain, and thus is a member of the hyaluronan-binding protein family. The hyaluronan-binding domain is known to be involved in extracellular matrix stability and cell migration. This protein has been shown to form a stable complex with inter-alpha-inhibitor (I alpha I), and thus enhance the serine protease inhibitory activity of I alpha I, which is important in the protease network associated with inflammation. This gene can be induced by proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-1. Enhanced levels of this protein are found in the synovial fluid of patients with osteoarthritis and rheumatoid arthritis.[provided by RefSeq, Dec 2010]

ENSG00000295625 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007115.4. 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
	TNFAIP6	NM_007115.4	MANE Select	c.232+498G>A		intron	N/A	NP_009046.2
	LOC101929319	NR_110248.1		n.306+8217C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP6	ENST00000243347.5	TSL:1 MANE Select	c.232+498G>A		intron	N/A	ENSP00000243347.3
	ENSG00000295625	ENST00000731384.1		n.176+8217C>T		intron	N/A
	ENSG00000295625	ENST00000731385.1		n.175+8217C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27344 AN: 151986 Hom.: 2818 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.180 AC: 27396 AN: 152104 Hom.: 2827 Cov.: 32 AF XY: 0.179 AC XY: 13316 AN XY: 74372

African (AFR) AF: 0.285 AC: 11835 AN: 41464

American (AMR) AF: 0.116 AC: 1777 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3466

East Asian (EAS) AF: 0.152 AC: 788 AN: 5170

South Asian (SAS) AF: 0.117 AC: 567 AN: 4828

European-Finnish (FIN) AF: 0.164 AC: 1736 AN: 10572

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9724 AN: 68002

Other (OTH) AF: 0.157 AC: 332 AN: 2108

Alfa AF: 0.175 Hom.: 347

Bravo AF: 0.183

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.66
PhyloP100		0.17
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: rs3755480; hg19: chr2-152221092;