14-92019537-G-T

Variant names:

• chr14-92019537-G-T
• rs7155279
• NM_004239.4:c.589-1787C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004239.4(TRIP11):​c.589-1787C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,000 control chromosomes in the GnomAD database, including 13,966 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 0.41 (13966 hom., cov: 32)
• Consequence: TRIP11 NM_004239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 41 publications found

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 Gene-Disease associations (from GenCC):

• achondrogenesis type IA

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet
• TRIP11-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP11	NM_004239.4	MANE Select	c.589-1787C>A		intron	N/A	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.586-1787C>A		intron	N/A	NP_001308780.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP11	ENST00000267622.8	TSL:1 MANE Select	c.589-1787C>A		intron	N/A	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000913145.1		c.586-1787C>A		intron	N/A	ENSP00000583204.1
	TRIP11	ENST00000913147.1		c.588+2019C>A		intron	N/A	ENSP00000583206.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62820 AN: 151880 Hom.: 13946 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.414 AC: 62881 AN: 152000 Hom.: 13966 Cov.: 32 AF XY: 0.409 AC XY: 30364 AN XY: 74286

African (AFR) AF: 0.585 AC: 24231 AN: 41420

American (AMR) AF: 0.274 AC: 4177 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3468

East Asian (EAS) AF: 0.364 AC: 1882 AN: 5176

South Asian (SAS) AF: 0.401 AC: 1934 AN: 4826

European-Finnish (FIN) AF: 0.339 AC: 3574 AN: 10548

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24355 AN: 67976

Other (OTH) AF: 0.387 AC: 818 AN: 2112

Alfa AF: 0.377 Hom.: 23443

Bravo AF: 0.417

Asia WGS AF: 0.422 AC: 1465 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		-0.13
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: rs7155279; hg19: chr14-92485881;