rs10432475

Variant names:

• chr2-151368426-A-G
• rs10432475
• NM_007115.4:c.395-1594A>G

Variant summary

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

The NM_007115.4(TNFAIP6):​c.395-1594A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 148,886 control chromosomes in the GnomAD database, including 603 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 0.079 (601 hom., cov: 26)
  • Exomes 𝑓: 0.088 (2 hom.)
• Consequence: TNFAIP6 NM_007115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• 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:):

MIR4773-2 (HGNC:41790): (microRNA 4773-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4773-1 (HGNC:41699): (microRNA 4773-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 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.395-1594A>G		intron	N/A	NP_009046.2
	LOC101929319	NR_110248.1		n.306+4369T>C		intron	N/A
	MIR4773-2	NR_039932.1		n.-15T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFAIP6	ENST00000243347.5	TSL:1 MANE Select	c.395-1594A>G		intron	N/A	ENSP00000243347.3	P98066
	TNFAIP6	ENST00000460812.1	TSL:3	n.77-1594A>G		intron	N/A
	ENSG00000295625	ENST00000731384.1		n.176+4369T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 11746 AN: 148542 Hom.: 601 Cov.: 26

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0669

Gnomad FIN AF: 0.0493

Gnomad MID AF: 0.0649

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0901

GnomAD2 exomes AF: 0.114 AC: 37 AN: 324 AF XY: 0.104

Gnomad AFR exome AF: 0.00

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.0877 AC: 20 AN: 228 Hom.: 2 Cov.: 0 AF XY: 0.100 AC XY: 10 AN XY: 100

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.113 AC: 19 AN: 168

Other (OTH) AF: 0.0556 AC: 1 AN: 18

GnomAD4 genome AF: 0.0790 AC: 11748 AN: 148658 Hom.: 601 Cov.: 26 AF XY: 0.0759 AC XY: 5518 AN XY: 72658

African (AFR) AF: 0.0242 AC: 991 AN: 41016

American (AMR) AF: 0.0662 AC: 996 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 371 AN: 3428

East Asian (EAS) AF: 0.170 AC: 837 AN: 4920

South Asian (SAS) AF: 0.0674 AC: 318 AN: 4716

European-Finnish (FIN) AF: 0.0493 AC: 471 AN: 9560

Middle Eastern (MID) AF: 0.0699 AC: 20 AN: 286

European-Non Finnish (NFE) AF: 0.111 AC: 7376 AN: 66736

Other (OTH) AF: 0.0906 AC: 188 AN: 2076

Alfa AF: 0.102 Hom.: 1074

Bravo AF: 0.0787

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.78
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: rs10432475; hg19: chr2-152224940;