rs3201475

Positions:

• chr8-125430484-C-T

Variant summary

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

The NM_025195.4(TRIB1):​c.-419C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 163,086 control chromosomes in the GnomAD database, including 6,311 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 0.25 (5790 hom., cov: 33)
  • Exomes 𝑓: 0.28 (521 hom.)
• Consequence: TRIB1 NM_025195.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

Genes affected

TRIB1 (HGNC:16891): (tribbles pseudokinase 1) Enables mitogen-activated protein kinase kinase binding activity and protein kinase inhibitor activity. Involved in several processes, including JNK cascade; negative regulation of lipopolysaccharide-mediated signaling pathway; and regulation of protein kinase activity. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIB1	NM_025195.4	c.-419C>T		5_prime_UTR_variant	1/3	ENST00000311922.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIB1	ENST00000311922.4	c.-419C>T		5_prime_UTR_variant	1/3	1	NM_025195.4	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37777 AN: 152050 Hom.: 5789 Cov.: 33

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.280 AC: 3057 AN: 10918 Hom.: 521 Cov.: 0 AF XY: 0.290 AC XY: 1681 AN XY: 5788

Gnomad4 AFR exome AF: 0.0605

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.248 AC: 37771 AN: 152168 Hom.: 5790 Cov.: 33 AF XY: 0.252 AC XY: 18756 AN XY: 74392

Gnomad4 AFR AF: 0.0664

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.270

Alfa AF: 0.294 Hom.: 1734

Bravo AF: 0.229

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs3201475; hg19: chr8-126442726; COSMIC: COSV61335675; COSMIC: COSV61335675;