rs113604435

Variant names:

• chr4-183663862-G-A
• rs113604435
• NM_021942.6:c.-6G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-183663862-G-A
• chr4-183663862-G-T

Variant summary

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

The NM_021942.6(TRAPPC11):​c.-6G>A variant causes a 5 prime UTR 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 NM_021942.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0560

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

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 id is 261440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183663862-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6	c.-6G>A		5_prime_UTR_variant	Exon 2 of 30	ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690	c.-6G>A		5_prime_UTR_variant	Exon 2 of 30	1	NM_021942.6	ENSP00000335371.6

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

Gnomad4 AFR exome AF: 0.103 AC: 3405 AN: 32992

Gnomad4 AMR exome AF: 0.0282 AC: 1242 AN: 44022

Gnomad4 ASJ exome AF: 0.0307 AC: 785 AN: 25594

Gnomad4 EAS exome AF: 0.000128 AC: 5 AN: 39092

Gnomad4 SAS exome AF: 0.00743 AC: 639 AN: 86028

Gnomad4 FIN exome AF: 0.0804 AC: 4244 AN: 52814

Gnomad4 NFE exome AF: 0.0340 AC: 37482 AN: 1103950

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.0992 AC: 0.0991878 AN: 0.0991878

Gnomad4 AMR AF: 0.0445 AC: 0.0445446 AN: 0.0445446

Gnomad4 ASJ AF: 0.0312 AC: 0.0311598 AN: 0.0311598

Gnomad4 EAS AF: 0.000197 AC: 0.000196773 AN: 0.000196773

Gnomad4 SAS AF: 0.00671 AC: 0.0067086 AN: 0.0067086

Gnomad4 FIN AF: 0.0887 AC: 0.0886676 AN: 0.0886676

Gnomad4 NFE AF: 0.0365 AC: 0.0364772 AN: 0.0364772

Gnomad4 OTH AF: 0.0491 AC: 0.0490944 AN: 0.0490944

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.81
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

Publications

LitVar

Other links and lift over

dbSNP: rs113604435; hg19: chr4-184585015;