rs8007661

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 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 -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 VariationId 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.

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.5160+195G>A		intron	N/A	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.5157+195G>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.5160+195G>A		intron	N/A	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000554357.5	TSL:1	c.4305+195G>A		intron	N/A	ENSP00000451032.1	H0YJ97
	TRIP11	ENST00000913145.1		c.5157+195G>A		intron	N/A	ENSP00000583204.1

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

African (AFR) AF: 0.695 AC: 28781 AN: 41402

American (AMR) AF: 0.336 AC: 5128 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1785 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2209 AN: 5170

South Asian (SAS) AF: 0.518 AC: 2494 AN: 4818

European-Finnish (FIN) AF: 0.477 AC: 5011 AN: 10504

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31622 AN: 67904

Other (OTH) AF: 0.486 AC: 1023 AN: 2106

Alfa AF: 0.480 Hom.: 85901

Bravo AF: 0.513

Asia WGS AF: 0.515 AC: 1789 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		-0.27
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: rs8007661; hg19: chr14-92459958; COSMIC: COSV50966107;