rs6889239

Variant names:

• chr5-151078210-T-C
• rs6889239
• NM_006058.5:c.-37+2670A>G

Variant summary

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

The NM_006058.5(TNIP1):​c.-37+2670A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,168 control chromosomes in the GnomAD database, including 15,905 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 0.41 (15905 hom., cov: 33)
• Consequence: TNIP1 NM_006058.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853
• Publications: 31 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 = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIP1	NM_006058.5	c.-37+2670A>G		intron_variant	Intron 1 of 17	ENST00000521591.6	NP_006049.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000521591.6	c.-37+2670A>G		intron_variant	Intron 1 of 17	1	NM_006058.5	ENSP00000430760.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62894 AN: 152050 Hom.: 15871 Cov.: 33

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.414 AC: 62983 AN: 152168 Hom.: 15905 Cov.: 33 AF XY: 0.418 AC XY: 31097 AN XY: 74402

African (AFR) AF: 0.682 AC: 28275 AN: 41472

American (AMR) AF: 0.421 AC: 6441 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3468

East Asian (EAS) AF: 0.730 AC: 3781 AN: 5180

South Asian (SAS) AF: 0.420 AC: 2029 AN: 4828

European-Finnish (FIN) AF: 0.286 AC: 3029 AN: 10602

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17108 AN: 67998

Other (OTH) AF: 0.385 AC: 813 AN: 2114

Alfa AF: 0.386 Hom.: 2105

Bravo AF: 0.439

Asia WGS AF: 0.544 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.35
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6889239; hg19: chr5-150457771;