rs587783180

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001253852.3(AP4B1):c.618-13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,610,424 control chromosomes in the GnomAD database, including 111,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9497 hom., cov: 32)

Exomes 𝑓: 0.36 ( 102173 hom. )

Consequence

AP4B1
NM_001253852.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0520

Variant links:

Genes affected

AP4B1 (HGNC:572): (adaptor related protein complex 4 subunit beta 1) This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AP4B1 links:

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

AP4B1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-113900413-C-G is Benign according to our data. Variant chr1-113900413-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 157725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-113900413-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP4B1	NM_001253852.3 link	c.618-13G>C		intron_variant	Intron 4 of 9	ENST00000369569.6	NP_001240781.1	Q9Y6B7-1A0A024R0J5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP4B1	ENST00000369569.6 link	c.618-13G>C		intron_variant	Intron 4 of 9	1	NM_001253852.3	ENSP00000358582.1		Q9Y6B7-1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48911

AN:

151986

Hom.:

9503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.765

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.339

GnomAD3 exomes

AF:

0.386

AC:

94825

AN:

245408

Hom.:

21222

AF XY:

0.376

AC XY:

50011

AN XY:

133074

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.521

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.773

Gnomad SAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.364

AC:

530324

AN:

1458320

Hom.:

102173

Cov.:

AF XY:

0.360

AC XY:

261163

AN XY:

725402

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.739

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.431

Gnomad4 NFE exome

AF:

0.360

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.322

AC:

48916

AN:

152104

Hom.:

9497

Cov.:

AF XY:

0.329

AC XY:

24494

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.461

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.764

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.324

Hom.:

1589

Bravo

AF:

0.323

Asia WGS

AF:

0.487

AC:

1692

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 22, 2016

GeneDx

Significance: 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. -

Dec 13, 2012

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hereditary spastic paraplegia 47

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.5

DANN

Benign

0.72

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