chr14-91968721-T-A

Position:

• chr14-91968721-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004239.4(TRIP11):​c.*952A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 227,620 control chromosomes in the GnomAD database, including 10,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6704 hom., cov: 32)
  • Exomes 𝑓: 0.33 (4246 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.107

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-91968721-T-A is Benign according to our data. Variant chr14-91968721-T-A is described in ClinVar as [Benign]. Clinvar id is 314902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP11	NM_004239.4	c.*952A>T		3_prime_UTR_variant	21/21	ENST00000267622.8	NP_004230.2
TRIP11	NM_001321851.1	c.*952A>T		3_prime_UTR_variant	21/21		NP_001308780.1
TRIP11	XM_047431935.1	c.*952A>T		3_prime_UTR_variant	13/13		XP_047287891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622	c.*952A>T		3_prime_UTR_variant	21/21	1	NM_004239.4	ENSP00000267622.4

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44326 AN: 151956 Hom.: 6705 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.329 AC: 24888 AN: 75546 Hom.: 4246 Cov.: 0 AF XY: 0.335 AC XY: 11673 AN XY: 34880

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.409

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.292 AC: 44332 AN: 152074 Hom.: 6704 Cov.: 32 AF XY: 0.291 AC XY: 21623 AN XY: 74330

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.288

Alfa AF: 0.127 Hom.: 226

Bravo AF: 0.279

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Achondrogenesis, type IA Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.81

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: rs1133441; hg19: chr14-92435065;