chr4-183663862-G-A

Variant names:

• chr4-183663862-G-A
• rs113604435
• ENST00000505676.5:n.-6G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000505676.5(TRAPPC11):​n.-6G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,600,768 control chromosomes in the GnomAD database, including 1,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (300 hom., cov: 31)
  • Exomes 𝑓: 0.035 (1125 hom.)
• Consequence: TRAPPC11 ENST00000505676.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0560
• Publications: 6 publications found

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]

TRAPPC11 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type R18

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet
• intellectual disability-hyperkinetic movement-truncal ataxia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• triple-A syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-183663862-G-A is Benign according to our data. Variant chr4-183663862-G-A is described in ClinVar as Benign. ClinVar VariationId is 261440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505676.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	NM_021942.6	MANE Select	c.-6G>A		5_prime_UTR	Exon 2 of 30	NP_068761.4
	TRAPPC11	NM_199053.3		c.-6G>A		5_prime_UTR	Exon 2 of 31	NP_951008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	ENST00000505676.5	TSL:1	n.-6G>A		non_coding_transcript_exon	Exon 2 of 19	ENSP00000422915.1
	TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.-6G>A		5_prime_UTR	Exon 2 of 30	ENSP00000335371.6
	TRAPPC11	ENST00000357207.8	TSL:1	c.-6G>A		5_prime_UTR	Exon 2 of 31	ENSP00000349738.4

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8386 AN: 150932 Hom.: 297 Cov.: 31

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0312

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00670

Gnomad FIN AF: 0.0887

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0491

GnomAD2 exomes AF: 0.0365 AC: 9137 AN: 250512 AF XY: 0.0344

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.0271

Gnomad ASJ exome AF: 0.0313

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0792

Gnomad NFE exome AF: 0.0361

Gnomad OTH exome AF: 0.0379

GnomAD4 exome AF: 0.0346 AC: 50203 AN: 1449720 Hom.: 1125 Cov.: 32 AF XY: 0.0337 AC XY: 24302 AN XY: 721132

African (AFR) AF: 0.103 AC: 3405 AN: 32992

American (AMR) AF: 0.0282 AC: 1242 AN: 44022

Ashkenazi Jewish (ASJ) AF: 0.0307 AC: 785 AN: 25594

East Asian (EAS) AF: 0.000128 AC: 5 AN: 39092

South Asian (SAS) AF: 0.00743 AC: 639 AN: 86028

European-Finnish (FIN) AF: 0.0804 AC: 4244 AN: 52814

Middle Eastern (MID) AF: 0.0380 AC: 215 AN: 5656

European-Non Finnish (NFE) AF: 0.0340 AC: 37482 AN: 1103950

Other (OTH) AF: 0.0367 AC: 2186 AN: 59572

GnomAD4 genome AF: 0.0557 AC: 8416 AN: 151048 Hom.: 300 Cov.: 31 AF XY: 0.0578 AC XY: 4262 AN XY: 73728

African (AFR) AF: 0.0992 AC: 4079 AN: 41124

American (AMR) AF: 0.0445 AC: 672 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.0312 AC: 108 AN: 3466

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5082

South Asian (SAS) AF: 0.00671 AC: 32 AN: 4770

European-Finnish (FIN) AF: 0.0887 AC: 917 AN: 10342

Middle Eastern (MID) AF: 0.0586 AC: 17 AN: 290

European-Non Finnish (NFE) AF: 0.0365 AC: 2476 AN: 67878

Other (OTH) AF: 0.0491 AC: 103 AN: 2098

Alfa AF: 0.0386 Hom.: 284

Bravo AF: 0.0529

Asia WGS AF: 0.0230 AC: 81 AN: 3478

EpiCase AF: 0.0363

EpiControl AF: 0.0353

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.81
PhyloP100		0.056
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs113604435; hg19: chr4-184585015;