rs736775

Variant names:

• chr5-151029787-T-C
• rs736775
• NM_006058.5:c.*926A>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.*926A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,924 control chromosomes in the GnomAD database, including 24,515 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 0.56 (24515 hom., cov: 30)
• Consequence: TNIP1 NM_006058.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 17 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP1	NM_006058.5	MANE Select	c.*926A>G		downstream_gene	N/A	NP_006049.3
	TNIP1	NM_001437741.1		c.*945A>G		downstream_gene	N/A	NP_001424670.1
	TNIP1	NM_001252390.2		c.*926A>G		downstream_gene	N/A	NP_001239319.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNIP1	ENST00000521591.6	TSL:1 MANE Select	c.*926A>G		downstream_gene	N/A	ENSP00000430760.1
	TNIP1	ENST00000315050.11	TSL:1	c.*926A>G		downstream_gene	N/A	ENSP00000317891.7
	TNIP1	ENST00000523338.5	TSL:1	c.*855A>G		downstream_gene	N/A	ENSP00000428243.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85050 AN: 151806 Hom.: 24497 Cov.: 30

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.560 AC: 85099 AN: 151924 Hom.: 24515 Cov.: 30 AF XY: 0.556 AC XY: 41281 AN XY: 74252

African (AFR) AF: 0.457 AC: 18910 AN: 41422

American (AMR) AF: 0.594 AC: 9071 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1785 AN: 5132

South Asian (SAS) AF: 0.400 AC: 1928 AN: 4816

European-Finnish (FIN) AF: 0.613 AC: 6478 AN: 10566

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43257 AN: 67936

Other (OTH) AF: 0.547 AC: 1157 AN: 2114

Alfa AF: 0.577 Hom.: 3783

Bravo AF: 0.555

Asia WGS AF: 0.403 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.37
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs736775; hg19: chr5-150409348; COSMIC: COSV59304668;