rs111785152

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001253852.3(AP4B1):c.898G>T(p.Val300Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

AP4B1
NM_001253852.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.04

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00972271).

BP6

Variant 1-113900120-C-A is Benign according to our data. Variant chr1-113900120-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 539528.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0011 (168/152306) while in subpopulation AFR AF = 0.00395 (164/41558). AF 95% confidence interval is 0.00345. There are 0 homozygotes in GnomAd4. There are 75 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP4B1	NM_001253852.3	MANE Select	c.898G>T	p.Val300Leu	missense	Exon 5 of 10	NP_001240781.1	Q9Y6B7-1
AP4B1	NM_001438373.1		c.898G>T	p.Val300Leu	missense	Exon 6 of 11	NP_001425302.1
AP4B1	NM_006594.5		c.898G>T	p.Val300Leu	missense	Exon 6 of 11	NP_006585.2	Q9Y6B7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP4B1	ENST00000369569.6	TSL:1 MANE Select	c.898G>T	p.Val300Leu	missense	Exon 5 of 10	ENSP00000358582.1	Q9Y6B7-1
AP4B1	ENST00000256658.8	TSL:1	c.898G>T	p.Val300Leu	missense	Exon 6 of 11	ENSP00000256658.4	Q9Y6B7-1
AP4B1	ENST00000863127.1		c.898G>T	p.Val300Leu	missense	Exon 5 of 11	ENSP00000533186.1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000270

AC:

AN:

251460

AF XY:

0.000177

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000958

AC:

140

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00349

AC:

117

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1112012

Other (OTH)

AF:

0.000132

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152306

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00395

AC:

164

AN:

41558

American (AMR)

AF:

0.000131

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000567

Hom.:

Bravo

AF:

0.00107

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000313

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 47 (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.071

Eigen

Benign

-0.087

Eigen_PC

Benign

0.094

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.010

MetaRNN

Benign

0.0097

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.28

PhyloP100

3.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.20

REVEL

Benign

0.12

Sift

Benign

0.13

Sift4G

Uncertain

0.045

Polyphen

0.083

Vest4

0.65

MutPred

0.63

Loss of catalytic residue at Q302 (P = 0.1408)

MVP

0.60

MPC

0.13

ClinPred

0.013

GERP RS

5.0

Varity_R

0.24

gMVP

0.45

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over