16-3676159-A-G

Position:

• chr16-3676159-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016292.3(TRAP1):​c.705-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,611,058 control chromosomes in the GnomAD database, including 665,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66318 hom., cov: 32)
  • Exomes 𝑓: 0.91 (598976 hom.)
• Consequence: TRAP1 NM_016292.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.548

Genes affected

TRAP1 (HGNC:16264): (TNF receptor associated protein 1) This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

DNASE1 (HGNC:2956): (deoxyribonuclease 1) This gene encodes a member of the DNase family. This protein is stored in the zymogen granules of the nuclear envelope and functions by cleaving DNA in an endonucleolytic manner. At least six autosomal codominant alleles have been characterized, DNASE1*1 through DNASE1*6, and the sequence of DNASE1*2 represented in this record. Mutations in this gene have been associated with systemic lupus erythematosus (SLE), an autoimmune disease. A recombinant form of this protein is used to treat the one of the symptoms of cystic fibrosis by hydrolyzing the extracellular DNA in sputum and reducing its viscosity. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

TRAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-3676159-A-G is Benign according to our data. Variant chr16-3676159-A-G is described in ClinVar as [Benign]. Clinvar id is 260709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAP1	NM_016292.3	c.705-14T>C		intron_variant		ENST00000246957.10	NP_057376.2
TRAP1	NM_001272049.2	c.546-14T>C		intron_variant			NP_001258978.1
TRAP1	XM_011522345.3	c.285-14T>C		intron_variant			XP_011520647.1
LOC124903630	XR_007064950.1	n.1666A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAP1	ENST00000246957.10	c.705-14T>C		intron_variant		1	NM_016292.3	ENSP00000246957.5

Frequencies

GnomAD3 genomes AF: 0.932 AC: 141829 AN: 152166 Hom.: 66255 Cov.: 32

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.928

GnomAD3 exomes AF: 0.932 AC: 231876 AN: 248890 Hom.: 108231 AF XY: 0.931 AC XY: 125370 AN XY: 134684

Gnomad AFR exome AF: 0.983

Gnomad AMR exome AF: 0.960

Gnomad ASJ exome AF: 0.941

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.983

Gnomad FIN exome AF: 0.911

Gnomad NFE exome AF: 0.894

Gnomad OTH exome AF: 0.924

GnomAD4 exome AF: 0.906 AC: 1321041 AN: 1458774 Hom.: 598976 Cov.: 33 AF XY: 0.908 AC XY: 658997 AN XY: 725738

Gnomad4 AFR exome AF: 0.985

Gnomad4 AMR exome AF: 0.957

Gnomad4 ASJ exome AF: 0.940

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.982

Gnomad4 FIN exome AF: 0.907

Gnomad4 NFE exome AF: 0.890

Gnomad4 OTH exome AF: 0.920

GnomAD4 genome AF: 0.932 AC: 141951 AN: 152284 Hom.: 66318 Cov.: 32 AF XY: 0.935 AC XY: 69584 AN XY: 74456

Gnomad4 AFR AF: 0.981

Gnomad4 AMR AF: 0.942

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.981

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.929

Alfa AF: 0.916 Hom.: 12160

Bravo AF: 0.936

Asia WGS AF: 0.990 AC: 3442 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.55

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: rs8050400; hg19: chr16-3726160; COSMIC: COSV55916788; COSMIC: COSV55916788;