5-151033641-C-T

Variant names:

• chr5-151033641-C-T
• rs62382331
• NM_006058.5:c.1746G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006058.5(TNIP1):​c.1746G>A​(p.Pro582Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 718,746 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (9 hom., cov: 27)
  • Exomes 𝑓: 0.020 (84 hom.)
• Consequence: TNIP1 NM_006058.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.28
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 5-151033641-C-T is Benign according to our data. Variant chr5-151033641-C-T is described in ClinVar as [Benign]. Clinvar id is 775226.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0134 (1424/106224) while in subpopulation AMR AF = 0.0214 (226/10570). AF 95% confidence interval is 0.0191. There are 9 homozygotes in GnomAd4. There are 672 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIP1	NM_006058.5	c.1746G>A	p.Pro582Pro	synonymous_variant	Exon 16 of 18	ENST00000521591.6	NP_006049.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000521591.6	c.1746G>A	p.Pro582Pro	synonymous_variant	Exon 16 of 18	1	NM_006058.5	ENSP00000430760.1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 1425 AN: 106170 Hom.: 9 Cov.: 27

Gnomad AFR AF: 0.00322

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00422

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0146

GnomAD2 exomes AF: 0.00936 AC: 1064 AN: 113694 AF XY: 0.0102

Gnomad AFR exome AF: 0.00213

Gnomad AMR exome AF: 0.00601

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00607

Gnomad NFE exome AF: 0.0140

Gnomad OTH exome AF: 0.00758

GnomAD4 exome AF: 0.0200 AC: 12230 AN: 612522 Hom.: 84 Cov.: 26 AF XY: 0.0198 AC XY: 5864 AN XY: 295790

African (AFR) AF: 0.00493 AC: 63 AN: 12784

American (AMR) AF: 0.0119 AC: 147 AN: 12404

Ashkenazi Jewish (ASJ) AF: 0.0200 AC: 147 AN: 7354

East Asian (EAS) AF: 0.000137 AC: 2 AN: 14568

South Asian (SAS) AF: 0.00545 AC: 107 AN: 19642

European-Finnish (FIN) AF: 0.0111 AC: 273 AN: 24656

Middle Eastern (MID) AF: 0.0182 AC: 45 AN: 2470

European-Non Finnish (NFE) AF: 0.0222 AC: 10977 AN: 495276

Other (OTH) AF: 0.0201 AC: 469 AN: 23368

GnomAD4 genome AF: 0.0134 AC: 1424 AN: 106224 Hom.: 9 Cov.: 27 AF XY: 0.0132 AC XY: 672 AN XY: 51102

African (AFR) AF: 0.00321 AC: 88 AN: 27374

American (AMR) AF: 0.0214 AC: 226 AN: 10570

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 42 AN: 2802

East Asian (EAS) AF: 0.00 AC: 0 AN: 3262

South Asian (SAS) AF: 0.00423 AC: 12 AN: 2838

European-Finnish (FIN) AF: 0.0114 AC: 64 AN: 5618

Middle Eastern (MID) AF: 0.0187 AC: 4 AN: 214

European-Non Finnish (NFE) AF: 0.0170 AC: 876 AN: 51480

Other (OTH) AF: 0.0144 AC: 20 AN: 1390

Alfa AF: 0.00962 Hom.: 0

Bravo AF: 0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.1
DANN	Benign	0.84
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs62382331; hg19: chr5-150413202; COSMIC: COSV59307317; COSMIC: COSV59307317;