rs2273188

Positions:

• chr14-92033137-G-A

Variant summary

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

The NM_004239.4(TRIP11):​c.201+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00688 in 1,319,654 control chromosomes in the GnomAD database, including 505 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 0.0085 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (444 hom.)
• Consequence: TRIP11 NM_004239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

Genes affected

TRIP11 (HGNC:12305): (thyroid hormone receptor interactor 11) This gene was identified based on the interaction of its protein product with thyroid hormone receptor beta. This protein is associated with the Golgi apparatus. The N-terminal region of the protein binds Golgi membranes and the C-terminal region binds the minus ends of microtubules; thus, the protein is thought to play a role in assembly and maintenance of the Golgi ribbon structure around the centrosome. Mutations in this gene cause achondrogenesis type IA.[provided by RefSeq, Mar 2010]

TRIP11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP11	NM_004239.4	c.201+55C>T		intron_variant		ENST00000267622.8	NP_004230.2
TRIP11	NM_001321851.1	c.198+55C>T		intron_variant			NP_001308780.1
TRIP11	XR_001750598.3	n.575+55C>T		intron_variant
TRIP11	XR_943560.3	n.575+55C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622.8	c.201+55C>T		intron_variant		1	NM_004239.4	ENSP00000267622.4
TRIP11	ENST00000555105.1	n.533+55C>T		intron_variant		1
TRIP11	ENST00000555516.6	c.-283+55C>T		intron_variant		5		ENSP00000451944.1

Frequencies

GnomAD3 genomes AF: 0.00851 AC: 1295 AN: 152096 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00666 AC: 7775 AN: 1167440 Hom.: 444 AF XY: 0.00582 AC XY: 3460 AN XY: 594736

Gnomad4 AFR exome AF: 0.00182

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.00124

Gnomad4 EAS exome AF: 0.0461

Gnomad4 SAS exome AF: 0.00234

Gnomad4 FIN exome AF: 0.000395

Gnomad4 NFE exome AF: 0.000242

Gnomad4 OTH exome AF: 0.00692

GnomAD4 genome AF: 0.00853 AC: 1298 AN: 152214 Hom.: 61 Cov.: 32 AF XY: 0.00962 AC XY: 716 AN XY: 74448

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.0576

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00413 Hom.: 1

Bravo AF: 0.0149

Asia WGS AF: 0.0300 AC: 105 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.27

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: rs2273188; hg19: chr14-92499481;