11-119019446-T-C

Position:

• chr11-119019446-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016146.6(TRAPPC4):​c.350+129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00821 in 1,062,892 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (296 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (167 hom.)
• Consequence: TRAPPC4 NM_016146.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-119019446-T-C is Benign according to our data. Variant chr11-119019446-T-C is described in ClinVar as [Benign]. Clinvar id is 1238350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC4	NM_016146.6	c.350+129T>C		intron_variant		ENST00000533632.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC4	ENST00000533632.6	c.350+129T>C		intron_variant		1	NM_016146.6	P1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5334 AN: 152046 Hom.: 297 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.0278

GnomAD4 exome AF: 0.00372 AC: 3389 AN: 910728 Hom.: 167 Cov.: 12 AF XY: 0.00331 AC XY: 1508 AN XY: 454962

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.00914

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000214

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000414

Gnomad4 OTH exome AF: 0.00856

GnomAD4 genome AF: 0.0351 AC: 5339 AN: 152164 Hom.: 296 Cov.: 32 AF XY: 0.0341 AC XY: 2540 AN XY: 74422

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.00628 Hom.: 5

Bravo AF: 0.0395

Asia WGS AF: 0.00779 AC: 27 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.50

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: rs190609010; hg19: chr11-118890156;