rs75987714

Positions:

• chr16-3695882-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TRAP1	NM_016292.3	c.89-4897G>C		intron_variant		ENST00000246957.10
TRAP1	NM_001272049.2	c.89-6745G>C		intron_variant
TRAP1	XM_011522345.3	c.-332-4897G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAP1	ENST00000246957.10	c.89-4897G>C		intron_variant		1	NM_016292.3	P1

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

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0612

Gnomad4 NFE AF: 0.0862

Gnomad4 OTH AF: 0.0596

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs75987714; hg19: chr16-3745883;