rs114748616

chr4-183679344-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_021942.6(TRAPPC11):c.832-9A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,558,362 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (24 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (21 hom.)
• Consequence: TRAPPC11 NM_021942.6 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001246
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.401

Genes affected

TRAPPC11 (HGNC:25751): (trafficking protein particle complex subunit 11) The protein encoded by this gene is a subunit of the TRAPP (transport protein particle) tethering complex, which functions in intracellular vesicle trafficking. This subunit is involved in early stage endoplasmic reticulum-to-Golgi vesicle transport. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-183679344-A-G is Benign according to our data. Variant chr4-183679344-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 448701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00893 (1359/152130) while in subpopulation AFR AF= 0.0311 (1292/41512). AF 95% confidence interval is 0.0297. There are 24 homozygotes in gnomad4. There are 641 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC11	NM_021942.6	c.832-9A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000334690.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC11	ENST00000334690.11	c.832-9A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_021942.6	P1
TRAPPC11	ENST00000357207.8	c.832-9A>G		splice_polypyrimidine_tract_variant, intron_variant		1
TRAPPC11	ENST00000505676.5	c.163-864A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00889 AC: 1351 AN: 152012 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00243 AC: 518 AN: 213072 Hom.: 8 AF XY: 0.00189 AC XY: 219 AN XY: 116062

Gnomad AFR exome AF: 0.0324

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000429

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000582

Gnomad OTH exome AF: 0.000822

GnomAD4 exome AF: 0.000884 AC: 1243 AN: 1406232 Hom.: 21 Cov.: 30 AF XY: 0.000771 AC XY: 537 AN XY: 696396

Gnomad4 AFR exome AF: 0.0334

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000524

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000358

Gnomad4 OTH exome AF: 0.00208

GnomAD4 genome AF: 0.00893 AC: 1359 AN: 152130 Hom.: 24 Cov.: 33 AF XY: 0.00862 AC XY: 641 AN XY: 74344

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00234 Hom.: 1

Bravo AF: 0.00972

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 15, 2020

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 03, 2020

- -

Autosomal recessive limb-girdle muscular dystrophy type R18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.5
Dann	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0
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: rs114748616; hg19: chr4-184600497;