rs114201291

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_StrongBS1BS2

The NM_001253852.3(AP4B1):c.1365T>C(p.Tyr455Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,614,204 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 24 hom., cov: 33)

Exomes 𝑓: 0.019 ( 324 hom. )

Consequence

AP4B1
NM_001253852.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.18

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-113896403-A-G is Benign according to our data. Variant chr1-113896403-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 157717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0143 (2183/152314) while in subpopulation NFE AF= 0.0229 (1560/68024). AF 95% confidence interval is 0.022. There are 24 homozygotes in gnomad4. There are 1012 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP4B1	NM_001253852.3 link	c.1365T>C	p.Tyr455Tyr	synonymous_variant	Exon 8 of 10	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.1365T>C	p.Tyr455Tyr	synonymous_variant	Exon 8 of 10	1	NM_001253852.3	ENSP00000358582.1		Q9Y6B7-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2183

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00400

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0229

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0152

AC:

3816

AN:

251280

Hom.:

AF XY:

0.0158

AC XY:

2148

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00758

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0243

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0195

AC:

28474

AN:

1461890

Hom.:

324

Cov.:

AF XY:

0.0195

AC XY:

14169

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00293

Gnomad4 AMR exome

AF:

0.0111

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00722

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.0227

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0143

AC:

2183

AN:

152314

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1012

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00399

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.0229

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0236

EpiControl

AF:

0.0236

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 01, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 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. -

Hereditary spastic paraplegia 47

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 07, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Hereditary spastic paraplegia

Benign:1

May 23, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.55

CADD

Benign

3.1

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

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