14-92019537-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP11	NM_004239.4	c.589-1787C>A		intron_variant		ENST00000267622.8
TRIP11	NM_001321851.1	c.586-1787C>A		intron_variant
TRIP11	XR_001750598.3	n.963-1787C>A		intron_variant, non_coding_transcript_variant
TRIP11	XR_943560.3	n.963-1787C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP11	ENST00000267622.8	c.589-1787C>A		intron_variant		1	NM_004239.4	P1
TRIP11	ENST00000555516.6	c.106-1787C>A		intron_variant		5

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

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.387

Alfa AF: 0.347 Hom.: 6707

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
Dann	Benign	0.64

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: rs7155279; hg19: chr14-92485881;