5-151078585-C-T

Variant names:

• chr5-151078585-C-T
• rs10036748
• NM_006058.5:c.-37+2295G>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.-37+2295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,060 control chromosomes in the GnomAD database, including 18,387 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 0.44 (18387 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNIP1 NM_006058.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 108 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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 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.-37+2295G>A		intron	N/A	NP_006049.3
	TNIP1	NM_001437741.1		c.-37+2295G>A		intron	N/A	NP_001424670.1
	TNIP1	NM_001252390.2		c.-37+9006G>A		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.-37+2295G>A		intron	N/A	ENSP00000430760.1	Q15025-1
	TNIP1	ENST00000315050.11	TSL:1	c.-37+8500G>A		intron	N/A	ENSP00000317891.7	Q15025-1
	TNIP1	ENST00000518977.5	TSL:1	c.-37+2295G>A		intron	N/A	ENSP00000430971.1	Q15025-2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66210 AN: 151942 Hom.: 18343 Cov.: 33

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.393

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.436 AC: 66313 AN: 152060 Hom.: 18387 Cov.: 33 AF XY: 0.439 AC XY: 32647 AN XY: 74294

African (AFR) AF: 0.764 AC: 31679 AN: 41488

American (AMR) AF: 0.430 AC: 6578 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1132 AN: 3468

East Asian (EAS) AF: 0.729 AC: 3777 AN: 5182

South Asian (SAS) AF: 0.420 AC: 2022 AN: 4820

European-Finnish (FIN) AF: 0.277 AC: 2923 AN: 10534

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

European-Non Finnish (NFE) AF: 0.250 AC: 17011 AN: 67966

Other (OTH) AF: 0.396 AC: 836 AN: 2110

Alfa AF: 0.312 Hom.: 42761

Bravo AF: 0.465

Asia WGS AF: 0.548 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		0.36
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: rs10036748; hg19: chr5-150458146;