rs11848512

Variant names:

• chr14-91967929-C-T
• rs11848512
• NM_004239.4:c.*1744G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004239.4(TRIP11):​c.*1744G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 200,694 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (295 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (16 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.350
• Publications: 0 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: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• TRIP11-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-91967929-C-T is Benign according to our data. Variant chr14-91967929-C-T is described in ClinVar as Benign. ClinVar VariationId is 314894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 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.*1744G>A		3_prime_UTR	Exon 21 of 21	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.*1744G>A		3_prime_UTR	Exon 21 of 21	NP_001308780.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP11	ENST00000267622.8	TSL:1 MANE Select	c.*1744G>A		3_prime_UTR	Exon 21 of 21	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000913145.1		c.*1744G>A		3_prime_UTR	Exon 21 of 21	ENSP00000583204.1

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5556 AN: 152062 Hom.: 292 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0376

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.00878 AC: 426 AN: 48514 Hom.: 16 Cov.: 0 AF XY: 0.00819 AC XY: 184 AN XY: 22458

African (AFR) AF: 0.103 AC: 208 AN: 2028

American (AMR) AF: 0.0127 AC: 18 AN: 1422

Ashkenazi Jewish (ASJ) AF: 0.000321 AC: 1 AN: 3114

East Asian (EAS) AF: 0.0111 AC: 85 AN: 7650

South Asian (SAS) AF: 0.0435 AC: 18 AN: 414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30

Middle Eastern (MID) AF: 0.00641 AC: 2 AN: 312

European-Non Finnish (NFE) AF: 0.00108 AC: 32 AN: 29590

Other (OTH) AF: 0.0157 AC: 62 AN: 3954

GnomAD4 genome AF: 0.0367 AC: 5589 AN: 152180 Hom.: 295 Cov.: 32 AF XY: 0.0361 AC XY: 2689 AN XY: 74386

African (AFR) AF: 0.118 AC: 4907 AN: 41490

American (AMR) AF: 0.0154 AC: 236 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0234 AC: 121 AN: 5182

South Asian (SAS) AF: 0.0372 AC: 179 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00100 AC: 68 AN: 68010

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.0750 Hom.: 38

Bravo AF: 0.0412

Asia WGS AF: 0.0670 AC: 231 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Achondrogenesis, type IA (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.23
PhyloP100		-0.35
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: rs11848512; hg19: chr14-92434273;