16-3696240-C-T

Position:

• chr16-3696240-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016292.3(TRAP1):​c.89-5255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,898 control chromosomes in the GnomAD database, including 16,781 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 0.43 (16781 hom., cov: 31)
• Consequence: TRAP1 NM_016292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAP1	NM_016292.3	c.89-5255G>A		intron_variant		ENST00000246957.10
TRAP1	NM_001272049.2	c.89-7103G>A		intron_variant
TRAP1	XM_011522345.3	c.-332-5255G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAP1	ENST00000246957.10	c.89-5255G>A		intron_variant		1	NM_016292.3	P1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65224 AN: 151780 Hom.: 16735 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.430 AC: 65337 AN: 151898 Hom.: 16781 Cov.: 31 AF XY: 0.428 AC XY: 31775 AN XY: 74248

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.415

Alfa AF: 0.320 Hom.: 16815

Bravo AF: 0.449

Asia WGS AF: 0.411 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.81
DANN	Benign	0.28
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: rs6500550; hg19: chr16-3746241;