rs4775912

Positions:

• chr15-50988782-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.2091-4588T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,118 control chromosomes in the GnomAD database, including 2,809 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 0.18 (2809 hom., cov: 32)
• Consequence: AP4E1 NM_007347.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP4E1	NM_007347.5	c.2091-4588T>C		intron_variant		ENST00000261842.10	NP_031373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP4E1	ENST00000261842.10	c.2091-4588T>C		intron_variant		1	NM_007347.5	ENSP00000261842	P1
AP4E1	ENST00000560508.1	c.1866-4588T>C		intron_variant		1		ENSP00000452976
AP4E1	ENST00000558439.5	c.*1215-4588T>C		intron_variant, NMD_transcript_variant		1		ENSP00000452712
AP4E1	ENST00000561393.5	c.*1135-4588T>C		intron_variant, NMD_transcript_variant		1		ENSP00000452711

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27659 AN: 152000 Hom.: 2809 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27665 AN: 152118 Hom.: 2809 Cov.: 32 AF XY: 0.182 AC XY: 13537 AN XY: 74360

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0177

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.203

Alfa AF: 0.176 Hom.: 3213

Bravo AF: 0.196

Asia WGS AF: 0.102 AC: 353 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.24

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: rs4775912; hg19: chr15-51280979;