rs3771892

Variant names:

• chr2-151361717-G-A
• rs3771892
• NM_007115.4:c.95-2226G>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.95-2226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,938 control chromosomes in the GnomAD database, including 2,842 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 (2842 hom., cov: 32)
• Consequence: TNFAIP6 NM_007115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP6	NM_007115.4	c.95-2226G>A		intron_variant	Intron 1 of 5	ENST00000243347.5	NP_009046.2
LOC101929319	NR_110248.1	n.306+11078C>T		intron_variant	Intron 2 of 2
TNFAIP6	XM_047445635.1	c.95-2226G>A		intron_variant	Intron 1 of 5		XP_047301591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP6	ENST00000243347.5	c.95-2226G>A		intron_variant	Intron 1 of 5	1	NM_007115.4	ENSP00000243347.3
ENSG00000295625	ENST00000731384.1	n.176+11078C>T		intron_variant	Intron 2 of 2
ENSG00000295625	ENST00000731385.1	n.175+11078C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27551 AN: 151822 Hom.: 2833 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.182 AC: 27599 AN: 151938 Hom.: 2842 Cov.: 32 AF XY: 0.180 AC XY: 13374 AN XY: 74266

African (AFR) AF: 0.291 AC: 12033 AN: 41380

American (AMR) AF: 0.118 AC: 1807 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3472

East Asian (EAS) AF: 0.151 AC: 778 AN: 5162

South Asian (SAS) AF: 0.118 AC: 570 AN: 4832

European-Finnish (FIN) AF: 0.164 AC: 1726 AN: 10544

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9714 AN: 67958

Other (OTH) AF: 0.160 AC: 336 AN: 2106

Alfa AF: 0.155 Hom.: 7692

Bravo AF: 0.185

Asia WGS AF: 0.140 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		0.44
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: rs3771892; hg19: chr2-152218231;