rs4507747

Variant names:

• chr8-140209026-C-T
• rs4507747
• NM_001160372.4:c.2556+12433G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

TRAPPC9 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 13

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual disability-obesity-brain malformations-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124902029 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.2556+12433G>A		intron_variant	Intron 17 of 22	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2556+12433G>A		intron_variant	Intron 17 of 22	1	NM_001160372.4	ENSP00000405060.3

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

African (AFR) AF: 0.313 AC: 12955 AN: 41436

American (AMR) AF: 0.460 AC: 7031 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3470

East Asian (EAS) AF: 0.00830 AC: 43 AN: 5178

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4814

European-Finnish (FIN) AF: 0.449 AC: 4730 AN: 10528

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.539 AC: 36601 AN: 67866

Other (OTH) AF: 0.419 AC: 883 AN: 2108

Alfa AF: 0.514 Hom.: 27742

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
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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