5-896868-A-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.388+74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,476,838 control chromosomes in the GnomAD database, including 34,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (13776 hom., cov: 32)
  • Exomes 𝑓: 0.13 (21112 hom.)
• Consequence: TRIP13 NM_004237.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.74

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=-0.93).
• BP6: Variant 5-896868-A-G is Benign according to our data. Variant chr5-896868-A-G is described in ClinVar as [Benign]. Clinvar id is 1278855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP13	NM_004237.4	c.388+74A>G		intron_variant		ENST00000166345.8
TRIP13	NM_001166260.2	c.388+74A>G		intron_variant
TRIP13	XM_011514163.2	c.388+74A>G		intron_variant
TRIP13	XM_047417879.1	c.-72+74A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP13	ENST00000166345.8	c.388+74A>G		intron_variant		1	NM_004237.4	P1
TRIP13	ENST00000512024.5	n.503+74A>G		intron_variant, non_coding_transcript_variant		1
TRIP13	ENST00000513435.1	c.375+74A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47625 AN: 151874 Hom.: 13711 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.0985

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.135 AC: 178224 AN: 1324846 Hom.: 21112 AF XY: 0.134 AC XY: 87412 AN XY: 651556

Gnomad4 AFR exome AF: 0.790

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.363

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.0958

Gnomad4 NFE exome AF: 0.0991

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.314 AC: 47757 AN: 151992 Hom.: 13776 Cov.: 32 AF XY: 0.312 AC XY: 23190 AN XY: 74306

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0986

Gnomad4 OTH AF: 0.263

Alfa AF: 0.133 Hom.: 3390

Bravo AF: 0.349

Asia WGS AF: 0.328 AC: 1139 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	-0.93
Cadd	Benign	0.041
Dann	Benign	0.49

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: rs920980; hg19: chr5-896983; COSMIC: COSV51319485; COSMIC: COSV51319485;