15-50908910-A-T

Position:

• chr15-50908910-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001252127.2(AP4E1):​c.-117A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,658 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AP4E1 NM_001252127.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.662

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 15-50908910-A-T is Benign according to our data. Variant chr15-50908910-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1111397.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP4E1	NM_007347.5	c.132A>T	p.Thr44Thr	synonymous_variant	1/21	ENST00000261842.10	NP_031373.2
AP4E1	NM_001252127.2	c.-117A>T		5_prime_UTR_premature_start_codon_gain_variant	1/21		NP_001239056.1
AP4E1	NM_001252127.2	c.-117A>T		5_prime_UTR_variant	1/21		NP_001239056.1
AP4E1	XM_005254264.5	c.-76+267A>T		intron_variant			XP_005254321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP4E1	ENST00000560508	c.-117A>T		5_prime_UTR_premature_start_codon_gain_variant	1/21	1		ENSP00000452976.1
AP4E1	ENST00000261842.10	c.132A>T	p.Thr44Thr	synonymous_variant	1/21	1	NM_007347.5	ENSP00000261842.5
AP4E1	ENST00000560508	c.-117A>T		5_prime_UTR_variant	1/21	1		ENSP00000452976.1
AP4E1	ENST00000561393.5	n.-117A>T		5_prime_UTR_premature_start_codon_gain_variant	1/20	1		ENSP00000452711.1
AP4E1	ENST00000558439.5	n.132A>T		non_coding_transcript_exon_variant	1/21	1		ENSP00000452712.1
AP4E1	ENST00000561393.5	n.-117A>T		non_coding_transcript_exon_variant	1/20	1		ENSP00000452711.1
AP4E1	ENST00000561393.5	n.-117A>T		5_prime_UTR_variant	1/20	1		ENSP00000452711.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458658 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725600

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spastic paraplegia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 27, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.6
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-51201107;