rs2235978

Variant names:

• chr14-92037924-C-A
• rs2235978
• NM_004239.4:c.139+1623G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-92037924-C-A
• chr14-92037924-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004239.4(TRIP11):​c.139+1623G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,980 control chromosomes in the GnomAD database, including 6,722 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 0.29 (6722 hom., cov: 32)
• Consequence: TRIP11 NM_004239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536
• Publications: 8 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, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Laboratory for Molecular Medicine
• TRIP11-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP11	NM_004239.4	c.139+1623G>T		intron_variant	Intron 1 of 20	ENST00000267622.8	NP_004230.2
TRIP11	NM_001321851.1	c.139+1623G>T		intron_variant	Intron 1 of 20		NP_001308780.1
TRIP11	XR_001750598.3	n.513+1623G>T		intron_variant	Intron 1 of 14
TRIP11	XR_943560.3	n.513+1623G>T		intron_variant	Intron 1 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP11	ENST00000267622.8	c.139+1623G>T		intron_variant	Intron 1 of 20	1	NM_004239.4	ENSP00000267622.4
TRIP11	ENST00000555105.1	n.471+1623G>T		intron_variant	Intron 1 of 2	1
TRIP11	ENST00000555516.6	c.-345+2956G>T		intron_variant	Intron 1 of 5	5		ENSP00000451944.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43697 AN: 151862 Hom.: 6702 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.288 AC: 43750 AN: 151980 Hom.: 6722 Cov.: 32 AF XY: 0.287 AC XY: 21303 AN XY: 74298

African (AFR) AF: 0.399 AC: 16544 AN: 41438

American (AMR) AF: 0.194 AC: 2968 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1084 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1838 AN: 5162

South Asian (SAS) AF: 0.351 AC: 1693 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2461 AN: 10548

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16269 AN: 67954

Other (OTH) AF: 0.275 AC: 578 AN: 2104

Alfa AF: 0.233 Hom.: 2329

Bravo AF: 0.289

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.55
PhyloP100		0.54
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: rs2235978; hg19: chr14-92504268;