chr5-151070675-T-C

Variant names:

• chr5-151070675-T-C
• rs4958881
• NM_006058.5:c.-36-5544A>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.-36-5544A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,154 control chromosomes in the GnomAD database, including 4,713 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 0.20 (4713 hom., cov: 32)
• Consequence: TNIP1 NM_006058.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.29
• Publications: 46 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIP1	NM_006058.5	c.-36-5544A>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.-36-5544A>G		intron_variant	Intron 1 of 17	1	NM_006058.5	ENSP00000430760.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30811 AN: 152036 Hom.: 4696 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0618

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.203 AC: 30861 AN: 152154 Hom.: 4713 Cov.: 32 AF XY: 0.199 AC XY: 14772 AN XY: 74392

African (AFR) AF: 0.440 AC: 18236 AN: 41480

American (AMR) AF: 0.131 AC: 1998 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3466

East Asian (EAS) AF: 0.0619 AC: 321 AN: 5186

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4826

European-Finnish (FIN) AF: 0.113 AC: 1203 AN: 10612

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7681 AN: 67986

Other (OTH) AF: 0.185 AC: 390 AN: 2112

Alfa AF: 0.147 Hom.: 5568

Bravo AF: 0.216

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.032
DANN	Benign	0.54
PhyloP100		-5.3
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: rs4958881; hg19: chr5-150450236;