rs3801246

Positions:

• chr7-98954344-C-T

Variant summary

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

The NM_001375524.1(TRRAP):​c.5731-754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,232 control chromosomes in the GnomAD database, including 41,679 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 0.70 (41679 hom., cov: 34)
• Consequence: TRRAP NM_001375524.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRRAP	NM_001375524.1	c.5731-754C>T		intron_variant		ENST00000456197.2	NP_001362453.1
TRRAP	NM_001244580.2	c.5710-754C>T		intron_variant			NP_001231509.1
TRRAP	NM_003496.4	c.5656-754C>T		intron_variant			NP_003487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRRAP	ENST00000456197.2	c.5731-754C>T		intron_variant		1	NM_001375524.1	ENSP00000394645.2

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106364 AN: 152114 Hom.: 41668 Cov.: 34

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.699 AC: 106388 AN: 152232 Hom.: 41679 Cov.: 34 AF XY: 0.703 AC XY: 52329 AN XY: 74440

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.746

Alfa AF: 0.771 Hom.: 8143

Bravo AF: 0.672

Asia WGS AF: 0.788 AC: 2743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.46

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: rs3801246; hg19: chr7-98551967;