7-98987529-G-T

Position:

• chr7-98987529-G-T

Variant summary

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

The NM_001375524.1(TRRAP):​c.9390-1236G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,172 control chromosomes in the GnomAD database, including 5,344 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 0.15 (5344 hom., cov: 33)
• Consequence: TRRAP NM_001375524.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525

Genes affected

TRRAP (HGNC:12347): (transformation/transcription domain associated protein) This gene encodes a large multidomain protein of the phosphoinositide 3-kinase-related kinases (PIKK) family. The encoded protein is a common component of many histone acetyltransferase (HAT) complexes and plays a role in transcription and DNA repair by recruiting HAT complexes to chromatin. Deregulation of this gene may play a role in several types of cancer including glioblastoma multiforme. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

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 (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRRAP	NM_001375524.1	c.9390-1236G>T		intron_variant		ENST00000456197.2
TRRAP	NM_001244580.2	c.9402-1236G>T		intron_variant
TRRAP	NM_003496.4	c.9315-1236G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRRAP	ENST00000456197.2	c.9390-1236G>T		intron_variant		1	NM_001375524.1	P2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22677 AN: 152054 Hom.: 5324 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0641

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.00757

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.149 AC: 22746 AN: 152172 Hom.: 5344 Cov.: 33 AF XY: 0.143 AC XY: 10664 AN XY: 74404

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.0639

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.00757

Gnomad4 OTH AF: 0.118

Alfa AF: 0.00707 Hom.: 16

Bravo AF: 0.170

Asia WGS AF: 0.0330 AC: 118 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	0.51
DANN	Benign	0.52

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: rs219818; hg19: chr7-98585152;