chr5-151060536-G-A

Variant names:

• chr5-151060536-G-A
• rs2233287
• NM_006058.5:c.358-141C>T

Variant summary

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

The NM_006058.5(TNIP1):​c.358-141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 706,374 control chromosomes in the GnomAD database, including 3,373 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 0.11 (1103 hom., cov: 32)
  • Exomes 𝑓: 0.083 (2270 hom.)
• Consequence: TNIP1 NM_006058.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 49 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006058.5. 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
	TNIP1	NM_006058.5	MANE Select	c.358-141C>T		intron	N/A	NP_006049.3
	TNIP1	NM_001437741.1		c.358-141C>T		intron	N/A	NP_001424670.1
	TNIP1	NM_001252390.2		c.358-141C>T		intron	N/A	NP_001239319.1	Q15025-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP1	ENST00000521591.6	TSL:1 MANE Select	c.358-141C>T		intron	N/A	ENSP00000430760.1	Q15025-1
	TNIP1	ENST00000315050.11	TSL:1	c.358-141C>T		intron	N/A	ENSP00000317891.7	Q15025-1
	TNIP1	ENST00000518977.5	TSL:1	c.358-141C>T		intron	N/A	ENSP00000430971.1	Q15025-2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16828 AN: 152122 Hom.: 1102 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0396

Gnomad FIN AF: 0.0685

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0887

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0827 AC: 45833 AN: 554132 Hom.: 2270 AF XY: 0.0809 AC XY: 23603 AN XY: 291752

African (AFR) AF: 0.192 AC: 2969 AN: 15484

American (AMR) AF: 0.0718 AC: 2117 AN: 29466

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 2004 AN: 16496

East Asian (EAS) AF: 0.000732 AC: 23 AN: 31420

South Asian (SAS) AF: 0.0523 AC: 2886 AN: 55226

European-Finnish (FIN) AF: 0.0669 AC: 2339 AN: 34982

Middle Eastern (MID) AF: 0.119 AC: 466 AN: 3920

European-Non Finnish (NFE) AF: 0.0896 AC: 30210 AN: 337292

Other (OTH) AF: 0.0945 AC: 2819 AN: 29846

GnomAD4 genome AF: 0.111 AC: 16845 AN: 152242 Hom.: 1103 Cov.: 32 AF XY: 0.107 AC XY: 7977 AN XY: 74438

African (AFR) AF: 0.185 AC: 7691 AN: 41542

American (AMR) AF: 0.0913 AC: 1397 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4824

European-Finnish (FIN) AF: 0.0685 AC: 727 AN: 10614

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0887 AC: 6028 AN: 67988

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.0958 Hom.: 3618

Bravo AF: 0.115

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.6
DANN	Benign	0.73
PhyloP100		2.0
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: rs2233287; hg19: chr5-150440097;