rs75987714

Variant names:

• chr16-3695882-C-G
• rs75987714
• NM_016292.3:c.89-4897G>C

Variant summary

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

The NM_016292.3(TRAP1):​c.89-4897G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 152,232 control chromosomes in the GnomAD database, including 348 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 0.056 (348 hom., cov: 32)
• Consequence: TRAP1 NM_016292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 4 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAP1	NM_016292.3	c.89-4897G>C		intron_variant	Intron 1 of 17	ENST00000246957.10	NP_057376.2
TRAP1	NM_001272049.2	c.89-6745G>C		intron_variant	Intron 1 of 16		NP_001258978.1
TRAP1	XM_011522345.3	c.-332-4897G>C		intron_variant	Intron 1 of 17		XP_011520647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAP1	ENST00000246957.10	c.89-4897G>C		intron_variant	Intron 1 of 17	1	NM_016292.3	ENSP00000246957.5

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8466 AN: 152114 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0862

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0556 AC: 8463 AN: 152232 Hom.: 348 Cov.: 32 AF XY: 0.0537 AC XY: 3995 AN XY: 74418

African (AFR) AF: 0.0162 AC: 675 AN: 41546

American (AMR) AF: 0.0515 AC: 788 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0220 AC: 106 AN: 4824

European-Finnish (FIN) AF: 0.0612 AC: 648 AN: 10596

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5864 AN: 68006

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0708 Hom.: 57

Bravo AF: 0.0539

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs75987714; hg19: chr16-3745883;