rs8007661

Variant names:

• chr14-91993614-C-T
• rs8007661
• NM_004239.4:c.5160+195G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004239.4(TRIP11):​c.5160+195G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,840 control chromosomes in the GnomAD database, including 21,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (21517 hom., cov: 31)
• Consequence: TRIP11 NM_004239.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.270

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 14-91993614-C-T is Benign according to our data. Variant chr14-91993614-C-T is described in ClinVar as [Benign]. Clinvar id is 667809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP11	NM_004239.4	c.5160+195G>A		intron_variant	Intron 15 of 20	ENST00000267622.8	NP_004230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622.8	c.5160+195G>A		intron_variant	Intron 15 of 20	1	NM_004239.4	ENSP00000267622.4
TRIP11	ENST00000554357.5	c.4305+195G>A		intron_variant	Intron 9 of 14	1		ENSP00000451032.1
TRIP11	ENST00000557017.1	n.408+195G>A		intron_variant	Intron 3 of 6	5		ENSP00000451607.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78577 AN: 151722 Hom.: 21501 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.518 AC: 78634 AN: 151840 Hom.: 21517 Cov.: 31 AF XY: 0.513 AC XY: 38037 AN XY: 74194

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.486

Alfa AF: 0.469 Hom.: 39521

Bravo AF: 0.513

Asia WGS AF: 0.515 AC: 1789 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.58

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: rs8007661; hg19: chr14-92459958; COSMIC: COSV50966107;