Genetic Variant AP4E1:c.-47C>A (chr15-50908732-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_007347.5(AP4E1):c.-47C>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 0.00000527 in 1,327,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

AP4E1
NM_007347.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0520

Variant links:

Genes affected

AP4E1 (HGNC:573): (adaptor related protein complex 4 subunit epsilon 1) This gene encodes a member of the adaptor complexes large subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is a large subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Disruption of this gene may be associated with cerebral palsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

AP4E1 links:

ENSG00000273674 (HGNC:):

ENSG00000273674 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 15-50908732-C-A is Benign according to our data. Variant chr15-50908732-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 388440.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AP4E1	NM_007347.5 link	c.-47C>A	5_prime_UTR_variant	Exon 1 of 21	ENST00000261842.10	NP_031373.2	Q9UPM8-1B4DM48
AP4E1	NM_001252127.2 link	c.-295C>A	5_prime_UTR_variant	Exon 1 of 21		NP_001239056.1	Q9UPM8-2B4DM48
AP4E1	XM_005254264.5 link	c.-76+89C>A	intron_variant	Intron 1 of 20		XP_005254321.1	Q9UPM8-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AP4E1	ENST00000261842 link	c.-47C>A	5_prime_UTR_variant	Exon 1 of 21	1	NM_007347.5	ENSP00000261842.5	Q9UPM8-1
AP4E1	ENST00000558439.5 link	n.-47C>A	non_coding_transcript_exon_variant	Exon 1 of 21	1		ENSP00000452712.1	H0YK95
AP4E1	ENST00000561393.5 link	n.-295C>A	non_coding_transcript_exon_variant	Exon 1 of 20	1		ENSP00000452711.1	H0YK94
AP4E1	ENST00000558439.5 link	n.-47C>A	5_prime_UTR_variant	Exon 1 of 21	1		ENSP00000452712.1	H0YK95
AP4E1	ENST00000561393.5 link	n.-295C>A	5_prime_UTR_variant	Exon 1 of 20	1		ENSP00000452711.1	H0YK94
AP4E1	ENST00000560508.1 link	c.-295C>A	upstream_gene_variant		1		ENSP00000452976.1	Q9UPM8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

88282

Hom.:

AF XY:

0.0000203

AC XY:

AN XY:

49358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000527

AC:

AN:

1327356

Hom.:

Cov.:

AF XY:

0.00000612

AC XY:

AN XY:

653436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000377

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000382

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 09, 2016

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over