Genetic Variant NM_007115.4:c.395-1594A>G (chr2-151368426-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.444

Publications

5 publications found

Variant links:

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]

TNFAIP6 links:

ENSG00000295625 (HGNC:):

ENSG00000295625 links:

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]

MIR4773-2 links:

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]

MIR4773-1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFAIP6	NM_007115.4 link	c.395-1594A>G		intron_variant	Intron 3 of 5	ENST00000243347.5	NP_009046.2	P98066

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFAIP6	ENST00000243347.5 link	c.395-1594A>G		intron_variant	Intron 3 of 5	1	NM_007115.4	ENSP00000243347.3		P98066

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

11746

AN:

148542

Hom.:

601

Cov.:

show subpopulations

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:

AN:

324

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.0877

AC:

AN:

228

Hom.:

Cov.:

AF XY:

0.100

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.113

AC:

AN:

168

Other (OTH)

AF:

0.0556

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0790

AC:

11748

AN:

148658

Hom.:

601

Cov.:

AF XY:

0.0759

AC XY:

5518

AN XY:

72658

show subpopulations

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:

AN:

286

European-Non Finnish (NFE)

AF:

0.111

AC:

7376

AN:

66736

Other (OTH)

AF:

0.0906

AC:

188

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

483

966

1449

1932

2415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.78

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over