rs74071653

Variant names:

• chr14-91968743-G-A
• rs74071653
• NM_004239.4:c.*930C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-91968743-G-A
• chr14-91968743-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004239.4(TRIP11):​c.*930C>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 0.0098 in 228,368 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (3 hom.)
• Consequence: TRIP11 NM_004239.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.362
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-91968743-G-A is Benign according to our data. Variant chr14-91968743-G-A is described in ClinVar as Benign. ClinVar VariationId is 314903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0132 (2009/152136) while in subpopulation AFR AF = 0.0453 (1879/41510). AF 95% confidence interval is 0.0436. There are 30 homozygotes in GnomAd4. There are 950 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

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.*930C>T		3_prime_UTR	Exon 21 of 21	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.*930C>T		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.*930C>T		3_prime_UTR	Exon 21 of 21	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000913145.1		c.*930C>T		3_prime_UTR	Exon 21 of 21	ENSP00000583204.1
	TRIP11	ENST00000876362.1		c.*930C>T		3_prime_UTR	Exon 20 of 20	ENSP00000546421.1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2007 AN: 152018 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00299 AC: 228 AN: 76232 Hom.: 3 Cov.: 0 AF XY: 0.00267 AC XY: 94 AN XY: 35220

African (AFR) AF: 0.0475 AC: 169 AN: 3556

American (AMR) AF: 0.00571 AC: 13 AN: 2278

Ashkenazi Jewish (ASJ) AF: 0.000209 AC: 1 AN: 4794

East Asian (EAS) AF: 0.00 AC: 0 AN: 10586

South Asian (SAS) AF: 0.00 AC: 0 AN: 656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1254

Middle Eastern (MID) AF: 0.00215 AC: 1 AN: 466

European-Non Finnish (NFE) AF: 0.000216 AC: 10 AN: 46372

Other (OTH) AF: 0.00542 AC: 34 AN: 6270

GnomAD4 genome AF: 0.0132 AC: 2009 AN: 152136 Hom.: 30 Cov.: 32 AF XY: 0.0128 AC XY: 950 AN XY: 74380

African (AFR) AF: 0.0453 AC: 1879 AN: 41510

American (AMR) AF: 0.00523 AC: 80 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67972

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00161 Hom.: 1

Bravo AF: 0.0151

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Achondrogenesis, type IA (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.37
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism

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: rs74071653; hg19: chr14-92435087;