11-119019112-C-G

Variant summary

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

The NM_016146.6(TRAPPC4):c.176-31C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 1,605,116 control chromosomes in the GnomAD database, including 8,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (653 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7806 hom.)
• Consequence: TRAPPC4 NM_016146.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.711

Genes affected

TRAPPC4 (HGNC:19943): (trafficking protein particle complex subunit 4) Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-119019112-C-G is Benign according to our data. Variant chr11-119019112-C-G is described in ClinVar as [Benign]. Clinvar id is 1282698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC4	NM_016146.6	c.176-31C>G		intron_variant		ENST00000533632.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC4	ENST00000533632.6	c.176-31C>G		intron_variant		1	NM_016146.6	P1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12864 AN: 152078 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.0656

GnomAD3 exomes AF: 0.0990 AC: 24402 AN: 246492 Hom.: 1521 AF XY: 0.107 AC XY: 14228 AN XY: 133302

Gnomad AFR exome AF: 0.0710

Gnomad AMR exome AF: 0.0618

Gnomad ASJ exome AF: 0.0402

Gnomad EAS exome AF: 0.0785

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.0835

Gnomad OTH exome AF: 0.0770

GnomAD4 exome AF: 0.0959 AC: 139405 AN: 1452920 Hom.: 7806 Cov.: 33 AF XY: 0.0996 AC XY: 71825 AN XY: 721148

Gnomad4 AFR exome AF: 0.0670

Gnomad4 AMR exome AF: 0.0619

Gnomad4 ASJ exome AF: 0.0399

Gnomad4 EAS exome AF: 0.0955

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.0882

Gnomad4 OTH exome AF: 0.0917

GnomAD4 genome AF: 0.0846 AC: 12876 AN: 152196 Hom.: 653 Cov.: 32 AF XY: 0.0888 AC XY: 6608 AN XY: 74396

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.0583

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.0787

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0834

Gnomad4 OTH AF: 0.0697

Alfa AF: 0.0361 Hom.: 35

Bravo AF: 0.0739

Asia WGS AF: 0.161 AC: 560 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.2
Dann	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3802882; hg19: chr11-118889822;