rs2233278

Positions:

• chr5-151087628-G-C
• chr5-151087628-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001252390.2(TNIP1):​c.-74C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 152,264 control chromosomes in the GnomAD database, including 265 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 0.051 (265 hom., cov: 32)
  • Exomes 𝑓: 0.025 (0 hom.)
• Consequence: TNIP1 NM_001252390.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIP1	NM_001252390.2	c.-74C>G		5_prime_UTR_variant	1/18		NP_001239319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000522226.5	c.-74C>G		5_prime_UTR_variant	1/18	2		ENSP00000428187	P3
TNIP1	ENST00000521001.1	c.-37+5810C>G		intron_variant		4		ENSP00000428404

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7724 AN: 152106 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.0936

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0250 AC: 1 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0333 AC XY: 1 AN XY: 30

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0313

GnomAD4 genome AF: 0.0507 AC: 7719 AN: 152224 Hom.: 265 Cov.: 32 AF XY: 0.0531 AC XY: 3955 AN XY: 74420

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.0928

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0596

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0566 Hom.: 33

Bravo AF: 0.0451

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2233278; hg19: chr5-150467189;