7-98881057-A-G

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.-61-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 1,019,080 control chromosomes in the GnomAD database, including 7,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (4280 hom., cov: 31)
  • Exomes 𝑓: 0.053 (3120 hom.)
• Consequence: TRRAP NM_001375524.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0740

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=-0.9).
• BP6: Variant 7-98881057-A-G is Benign according to our data. Variant chr7-98881057-A-G is described in ClinVar as [Benign]. Clinvar id is 1222828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRRAP	NM_001375524.1	c.-61-33A>G		intron_variant		ENST00000456197.2
TRRAP	NM_001244580.2	c.-61-33A>G		intron_variant
TRRAP	NM_003496.4	c.-61-33A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRRAP	ENST00000456197.2	c.-61-33A>G		intron_variant		1	NM_001375524.1	P2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23633 AN: 152066 Hom.: 4255 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.0527 AC: 45712 AN: 866896 Hom.: 3120 Cov.: 11 AF XY: 0.0522 AC XY: 22921 AN XY: 438950

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.0493

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.000247

Gnomad4 SAS exome AF: 0.0557

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0419

Gnomad4 OTH exome AF: 0.0724

GnomAD4 genome AF: 0.156 AC: 23702 AN: 152184 Hom.: 4280 Cov.: 31 AF XY: 0.151 AC XY: 11266 AN XY: 74422

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0600 Hom.: 685

Bravo AF: 0.171

Asia WGS AF: 0.0530 AC: 185 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 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.63
Dann	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6465726; hg19: chr7-98478680;