rs75712687

Variant names:

• chr16-3695272-G-A
• rs75712687
• NM_016292.3:c.89-4287C>T

Variant summary

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

The ENST00000246957.10(TRAP1):​c.89-4287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,184 control chromosomes in the GnomAD database, including 1,339 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 0.11 (1339 hom., cov: 31)
• Consequence: TRAP1 ENST00000246957.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000246957.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAP1	NM_016292.3	MANE Select	c.89-4287C>T		intron	N/A	NP_057376.2
	TRAP1	NM_001272049.2		c.89-6135C>T		intron	N/A	NP_001258978.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAP1	ENST00000246957.10	TSL:1 MANE Select	c.89-4287C>T		intron	N/A	ENSP00000246957.5
	TRAP1	ENST00000538171.5	TSL:2	c.89-6135C>T		intron	N/A	ENSP00000442070.1
	TRAP1	ENST00000570403.1	TSL:4	n.*159-4287C>T		intron	N/A	ENSP00000461354.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17243 AN: 152066 Hom.: 1337 Cov.: 31

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.113 AC: 17238 AN: 152184 Hom.: 1339 Cov.: 31 AF XY: 0.111 AC XY: 8294 AN XY: 74400

African (AFR) AF: 0.0299 AC: 1242 AN: 41518

American (AMR) AF: 0.0952 AC: 1455 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 626 AN: 3470

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5180

South Asian (SAS) AF: 0.117 AC: 562 AN: 4818

European-Finnish (FIN) AF: 0.125 AC: 1328 AN: 10594

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11559 AN: 68006

Other (OTH) AF: 0.117 AC: 248 AN: 2112

Alfa AF: 0.150 Hom.: 384

Bravo AF: 0.106

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		0.48
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: rs75712687; hg19: chr16-3745273;