Genetic Variant TRIP11:c.589-1787C>A (chr14-92019537-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

Publications

41 publications found

Variant links:

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

TRIP11 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRIP11	NM_004239.4 link	c.589-1787C>A	intron_variant	Intron 4 of 20	ENST00000267622.8	NP_004230.2	Q15643-1
TRIP11	NM_001321851.1 link	c.586-1787C>A	intron_variant	Intron 4 of 20		NP_001308780.1
TRIP11	XR_001750598.3 link	n.963-1787C>A	intron_variant	Intron 4 of 14
TRIP11	XR_943560.3 link	n.963-1787C>A	intron_variant	Intron 4 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622.8 link	c.589-1787C>A		intron_variant	Intron 4 of 20	1	NM_004239.4	ENSP00000267622.4		Q15643-1
TRIP11	ENST00000555516.6 link	c.106-1787C>A		intron_variant	Intron 4 of 5	5		ENSP00000451944.1		G3V4R7

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62820

AN:

151880

Hom.:

13946

Cov.:

show subpopulations

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.:

AF XY:

0.409

AC XY:

30364

AN XY:

74286

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1838

3677

5515

7354

9192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.3

(source)

DANN

Benign

0.64

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over