rs4507747

chr8-140209026-C-T

Variant summary

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

The NM_001160372.4(TRAPPC9):c.2556+12433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,884 control chromosomes in the GnomAD database, including 15,870 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 0.44 (15870 hom., cov: 32)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

Genes affected

TRAPPC9 (HGNC:30832): (trafficking protein particle complex subunit 9) This gene encodes a protein that likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive cognitive disability. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

LOC124902029 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.2556+12433G>A		intron_variant		ENST00000438773.4
LOC124902029	XR_007061118.1	n.8928C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2556+12433G>A		intron_variant		1	NM_001160372.4	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66089 AN: 151766 Hom.: 15854 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.435 AC: 66136 AN: 151884 Hom.: 15870 Cov.: 32 AF XY: 0.426 AC XY: 31620 AN XY: 74198

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.419

Alfa AF: 0.514 Hom.: 18167

Bravo AF: 0.438

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.0
Dann	Benign	0.84

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: rs4507747; hg19: chr8-141219125; COSMIC: COSV66902813;