rs2108430

Variant names:

• chr16-3688077-C-T
• rs2108430
• NM_016292.3:c.330+978G>A

Variant summary

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

The NM_016292.3(TRAP1):​c.330+978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,880 control chromosomes in the GnomAD database, including 11,712 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 0.37 (11712 hom., cov: 30)
• Consequence: TRAP1 NM_016292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 6 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]

TRAP1 Gene-Disease associations (from GenCC):

• syndromic disease

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016292.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAP1	NM_016292.3	MANE Select	c.330+978G>A		intron	N/A	NP_057376.2	Q12931-1
	TRAP1	NM_001272049.2		c.171+978G>A		intron	N/A	NP_001258978.1	Q12931-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAP1	ENST00000246957.10	TSL:1 MANE Select	c.330+978G>A		intron	N/A	ENSP00000246957.5	Q12931-1
	TRAP1	ENST00000900180.1		c.330+978G>A		intron	N/A	ENSP00000570239.1
	TRAP1	ENST00000923089.1		c.330+978G>A		intron	N/A	ENSP00000593148.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55678 AN: 151762 Hom.: 11683 Cov.: 30

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.367 AC: 55775 AN: 151880 Hom.: 11712 Cov.: 30 AF XY: 0.365 AC XY: 27100 AN XY: 74224

African (AFR) AF: 0.583 AC: 24141 AN: 41396

American (AMR) AF: 0.318 AC: 4851 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1908 AN: 5152

South Asian (SAS) AF: 0.338 AC: 1628 AN: 4810

European-Finnish (FIN) AF: 0.232 AC: 2445 AN: 10556

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18373 AN: 67944

Other (OTH) AF: 0.372 AC: 784 AN: 2110

Alfa AF: 0.331 Hom.: 1163

Bravo AF: 0.384

Asia WGS AF: 0.395 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.29
DANN	Benign	0.32
PhyloP100		-1.7
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: rs2108430; hg19: chr16-3738078;