chr5-151059427-C-T

Variant names:

• chr5-151059427-C-T
• rs1422673
• NM_006058.5:c.435+891G>A

Variant summary

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

The NM_006058.5(TNIP1):​c.435+891G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,068 control chromosomes in the GnomAD database, including 6,238 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 0.27 (6238 hom., cov: 32)
• Consequence: TNIP1 NM_006058.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 21 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=-1.19).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIP1	NM_006058.5	c.435+891G>A		intron_variant	Intron 5 of 17	ENST00000521591.6	NP_006049.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000521591.6	c.435+891G>A		intron_variant	Intron 5 of 17	1	NM_006058.5	ENSP00000430760.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40969 AN: 151950 Hom.: 6227 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.270 AC: 41014 AN: 152068 Hom.: 6238 Cov.: 32 AF XY: 0.272 AC XY: 20234 AN XY: 74340

African (AFR) AF: 0.352 AC: 14573 AN: 41448

American (AMR) AF: 0.360 AC: 5504 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2707 AN: 5170

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4820

European-Finnish (FIN) AF: 0.173 AC: 1828 AN: 10596

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.193 AC: 13121 AN: 67972

Other (OTH) AF: 0.271 AC: 572 AN: 2110

Alfa AF: 0.226 Hom.: 13278

Bravo AF: 0.291

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.24
DANN	Benign	0.32
PhyloP100		-2.2
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: rs1422673; hg19: chr5-150438988;