5-896611-C-G

Variant summary

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

The NM_004237.4(TRIP13):c.259-54C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 1,567,272 control chromosomes in the GnomAD database, including 10,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (4612 hom., cov: 33)
  • Exomes 𝑓: 0.062 (5841 hom.)
• Consequence: TRIP13 NM_004237.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.125

Genes affected

TRIP13 (HGNC:12307): (thyroid hormone receptor interactor 13) This gene encodes a protein that interacts with thyroid hormone receptors, also known as hormone-dependent transcription factors. The gene product interacts specifically with the ligand binding domain. This gene is one of several that may play a role in early-stage non-small cell lung cancer. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-896611-C-G is Benign according to our data. Variant chr5-896611-C-G is described in ClinVar as [Benign]. Clinvar id is 1282991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP13	NM_004237.4	c.259-54C>G		intron_variant		ENST00000166345.8
TRIP13	NM_001166260.2	c.259-54C>G		intron_variant
TRIP13	XM_011514163.2	c.259-54C>G		intron_variant
TRIP13	XM_047417879.1	c.-201-54C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP13	ENST00000166345.8	c.259-54C>G		intron_variant		1	NM_004237.4	P1
TRIP13	ENST00000512024.5	n.374-54C>G		intron_variant, non_coding_transcript_variant		1
TRIP13	ENST00000513435.1	c.246-54C>G		intron_variant		5
TRIP13	ENST00000508456.1	n.233-99C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25217 AN: 152042 Hom.: 4587 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0616 AC: 87162 AN: 1415112 Hom.: 5841 AF XY: 0.0602 AC XY: 42094 AN XY: 699286

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.0448

Gnomad4 ASJ exome AF: 0.0734

Gnomad4 EAS exome AF: 0.00240

Gnomad4 SAS exome AF: 0.0518

Gnomad4 FIN exome AF: 0.0599

Gnomad4 NFE exome AF: 0.0515

Gnomad4 OTH exome AF: 0.0774

GnomAD4 genome AF: 0.166 AC: 25291 AN: 152160 Hom.: 4612 Cov.: 33 AF XY: 0.161 AC XY: 11996 AN XY: 74398

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.0712

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.125

Alfa AF: 0.123 Hom.: 366

Bravo AF: 0.180

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.18

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: rs7708206; hg19: chr5-896726;