Variant rs12146493 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138368.5(AP5B1):c.631C>T(p.Leu211Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,596,254 control chromosomes in the GnomAD database, including 83,908 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 0.33 ( 9020 hom., cov: 33)

Exomes 𝑓: 0.32 ( 74888 hom. )

Consequence

AP5B1
NM_138368.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.843

Variant links:

Genes affected

AP5B1 (HGNC:25104): (adaptor related protein complex 5 subunit beta 1) Involved in endosomal transport. Located in lysosomal membrane. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

AP5B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033432245).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP5B1	NM_138368.5 linkuse as main transcript	c.631C>T	p.Leu211Phe	missense_variant	2/2	ENST00000532090.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP5B1	ENST00000532090.3 linkuse as main transcript	c.631C>T	p.Leu211Phe	missense_variant	2/2	1	NM_138368.5	P1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50749

AN:

152034

Hom.:

9008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.318

GnomAD3 exomes

AF:

0.277

AC:

64083

AN:

231324

Hom.:

9784

AF XY:

0.270

AC XY:

34031

AN XY:

126014

show subpopulations

Gnomad AFR exome

AF:

0.434

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.319

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.315

AC:

455589

AN:

1444102

Hom.:

74888

Cov.:

AF XY:

0.309

AC XY:

221741

AN XY:

717680

show subpopulations

Gnomad4 AFR exome

AF:

0.436

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.321

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.276

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.316

GnomAD4 genome

AF:

0.334

AC:

50794

AN:

152152

Hom.:

9020

Cov.:

AF XY:

0.324

AC XY:

24136

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.434

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.327

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.323

Gnomad4 OTH

AF:

0.315

Alfa

AF:

0.326

Hom.:

7741

Bravo

AF:

0.345

TwinsUK

AF:

0.332

AC:

1231

ALSPAC

AF:

0.333

AC:

1282

ESP6500AA

AF:

0.414

AC:

1619

ESP6500EA

AF:

0.320

AC:

2644

ExAC

AF:

0.287

AC:

34619

Asia WGS

AF:

0.269

AC:

937

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.27

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0084

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0033

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.7

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.14

MPC

0.41

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.36

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over