rs3755480

Positions:

• chr2-151364578-G-A
• chr2-151364578-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC101929319 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFAIP6	NM_007115.4	c.232+498G>A		intron_variant		ENST00000243347.5	NP_009046.2
TNFAIP6	XM_047445635.1	c.232+498G>A		intron_variant			XP_047301591.1
LOC101929319	NR_110248.1	n.306+8217C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFAIP6	ENST00000243347.5	c.232+498G>A		intron_variant		1	NM_007115.4	ENSP00000243347.3

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

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.157

Alfa AF: 0.170 Hom.: 317

Bravo AF: 0.183

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.66

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: rs3755480; hg19: chr2-152221092;