15-51004210-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007347.5(AP4E1):c.*1548T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,946 control chromosomes in the GnomAD database, including 27,435 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27416 hom., cov: 31)
  • Exomes 𝑓: 0.85 (19 hom.)
• Consequence: AP4E1 NM_007347.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP4E1	NM_007347.5	c.*1548T>C		3_prime_UTR_variant	21/21	ENST00000261842.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP4E1	ENST00000261842.10	c.*1548T>C		3_prime_UTR_variant	21/21	1	NM_007347.5	P1
AP4E1	ENST00000560508.1	c.*1548T>C		3_prime_UTR_variant	21/21	1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90898 AN: 151776 Hom.: 27370 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.846 AC: 44 AN: 52 Hom.: 19 Cov.: 0 AF XY: 0.875 AC XY: 28 AN XY: 32

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.933

Gnomad4 NFE exome AF: 0.722

GnomAD4 genome AF: 0.599 AC: 91004 AN: 151894 Hom.: 27416 Cov.: 31 AF XY: 0.594 AC XY: 44056 AN XY: 74218

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.592

Alfa AF: 0.607 Hom.: 37094

Bravo AF: 0.588

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.98
Dann	Benign	0.73

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: rs714784; hg19: chr15-51296407;