7-98882084-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001375524.1(TRRAP):c.150+60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,400,722 control chromosomes in the GnomAD database, including 394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (230 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (164 hom.)
• Consequence: TRRAP NM_001375524.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.80

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-98882084-G-A is Benign according to our data. Variant chr7-98882084-G-A is described in ClinVar as [Benign]. Clinvar id is 1287771.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRRAP	NM_001375524.1	c.150+60G>A		intron_variant		ENST00000456197.2
TRRAP	NM_001244580.2	c.150+60G>A		intron_variant
TRRAP	NM_003496.4	c.150+60G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRRAP	ENST00000456197.2	c.150+60G>A		intron_variant		1	NM_001375524.1	P2

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4530 AN: 151970 Hom.: 230 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.00321 AC: 4011 AN: 1248634 Hom.: 164 AF XY: 0.00281 AC XY: 1760 AN XY: 625658

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.00845

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000216

Gnomad4 FIN exome AF: 0.0000200

Gnomad4 NFE exome AF: 0.000418

Gnomad4 OTH exome AF: 0.00691

GnomAD4 genome AF: 0.0298 AC: 4537 AN: 152088 Hom.: 230 Cov.: 32 AF XY: 0.0284 AC XY: 2108 AN XY: 74356

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0236 Hom.: 20

Bravo AF: 0.0344

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.0030
Dann	Benign	0.47

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: rs6963893; hg19: chr7-98479707;