2-151368426-A-G

Position:

• chr2-151368426-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TNFAIP6	NM_007115.4	c.395-1594A>G		intron_variant		ENST00000243347.5
LOC101929319	NR_110248.1	n.306+4369T>C		intron_variant, non_coding_transcript_variant
MIR4773-2	NR_039932.1			upstream_gene_variant
MIR4773-1	NR_039931.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFAIP6	ENST00000243347.5	c.395-1594A>G		intron_variant		1	NM_007115.4	P1
TNFAIP6	ENST00000460812.1	n.77-1594A>G		intron_variant, non_coding_transcript_variant		3
MIR4773-2	ENST00000637203.1			upstream_gene_variant
MIR4773-1	ENST00000585225.1			downstream_gene_variant

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

GnomAD3 exomes AF: 0.114 AC: 37 AN: 324 Hom.: 5 AF XY: 0.104 AC XY: 19 AN XY: 182

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.0556

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

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0662

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.0674

Gnomad4 FIN AF: 0.0493

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0906

Alfa AF: 0.106 Hom.: 873

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
DANN	Benign	0.78

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: rs10432475; hg19: chr2-152224940;