5-151089865-C-T

Variant names:

• chr5-151089865-C-T
• rs3762999
• ENST00000521001.2:c.-37+3573G>A

Variant summary

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

The ENST00000521001.2(TNIP1):​c.-37+3573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,944 control chromosomes in the GnomAD database, including 18,837 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 0.49 (18837 hom., cov: 33)
• Consequence: TNIP1 ENST00000521001.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 15 publications found

Genes affected

TNIP1 (HGNC:16903): (TNFAIP3 interacting protein 1) This gene encodes an A20-binding protein which plays a role in autoimmunity and tissue homeostasis through the regulation of nuclear factor kappa-B activation. Mutations in this gene have been associated with psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

TNIP1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521001.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP1	ENST00000521001.2	TSL:4	c.-37+3573G>A		intron	N/A	ENSP00000428404.2	E7EWG2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74741 AN: 151826 Hom.: 18801 Cov.: 33

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.492 AC: 74831 AN: 151944 Hom.: 18837 Cov.: 33 AF XY: 0.498 AC XY: 36960 AN XY: 74264

African (AFR) AF: 0.533 AC: 22061 AN: 41428

American (AMR) AF: 0.536 AC: 8192 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1639 AN: 3468

East Asian (EAS) AF: 0.734 AC: 3793 AN: 5168

South Asian (SAS) AF: 0.607 AC: 2922 AN: 4814

European-Finnish (FIN) AF: 0.454 AC: 4787 AN: 10540

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29910 AN: 67940

Other (OTH) AF: 0.475 AC: 1002 AN: 2108

Alfa AF: 0.467 Hom.: 53246

Bravo AF: 0.502

Asia WGS AF: 0.581 AC: 2021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3762999;

hg19: chr5-150469426;