16-3688285-G-T

Position:

• chr16-3688285-G-T

Variant summary

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

The NM_016292.3(TRAP1):​c.330+770C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,844 control chromosomes in the GnomAD database, including 2,561 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 0.18 (2561 hom., cov: 30)
• Consequence: TRAP1 NM_016292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAP1	NM_016292.3	c.330+770C>A		intron_variant		ENST00000246957.10	NP_057376.2
TRAP1	NM_001272049.2	c.171+770C>A		intron_variant			NP_001258978.1
TRAP1	XM_011522345.3	c.-91+770C>A		intron_variant			XP_011520647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAP1	ENST00000246957.10	c.330+770C>A		intron_variant		1	NM_016292.3	ENSP00000246957	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27436 AN: 151726 Hom.: 2555 Cov.: 30

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.181 AC: 27479 AN: 151844 Hom.: 2561 Cov.: 30 AF XY: 0.181 AC XY: 13396 AN XY: 74196

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.189

Alfa AF: 0.184 Hom.: 547

Bravo AF: 0.180

Asia WGS AF: 0.189 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72778151; hg19: chr16-3738286;