NM_006058.5:c.*926A>G

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIP1	NM_006058.5	c.*926A>G		downstream_gene_variant		ENST00000521591.6	NP_006049.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000521591.6	c.*926A>G		downstream_gene_variant		1	NM_006058.5	ENSP00000430760.1

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 v4.3

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;