dbSNP rs12146493: AP5B1:p.Leu211Phe (chr11-65779862-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

42 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AP5B1	NM_138368.5 link	c.631C>T	p.Leu211Phe	missense_variant	Exon 2 of 2	ENST00000532090.3	NP_612377.4	Q2VPB7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP5B1	ENST00000532090.3 link	c.631C>T	p.Leu211Phe	missense_variant	Exon 2 of 2	1	NM_138368.5	ENSP00000454303.1		Q2VPB7

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

GnomAD2 exomes

AF:

0.277

AC:

64083

AN:

231324

AF XY:

0.270

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 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

African (AFR)

AF:

0.436

AC:

14373

AN:

32964

American (AMR)

AF:

0.217

AC:

9247

AN:

42634

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

6297

AN:

24602

East Asian (EAS)

AF:

0.321

AC:

12746

AN:

39650

South Asian (SAS)

AF:

0.112

AC:

9433

AN:

84320

European-Finnish (FIN)

AF:

0.276

AC:

14208

AN:

51478

Middle Eastern (MID)

AF:

0.303

AC:

1714

AN:

5664

European-Non Finnish (NFE)

AF:

0.334

AC:

368756

AN:

1103198

Other (OTH)

AF:

0.316

AC:

18815

AN:

59592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

21062

42125

63187

84250

105312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.334

AC:

50794

AN:

152152

Hom.:

9020

Cov.:

AF XY:

0.324

AC XY:

24136

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.434

AC:

18028

AN:

41494

American (AMR)

AF:

0.258

AC:

3946

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

958

AN:

3470

East Asian (EAS)

AF:

0.327

AC:

1692

AN:

5168

South Asian (SAS)

AF:

0.114

AC:

551

AN:

4834

European-Finnish (FIN)

AF:

0.251

AC:

2659

AN:

10600

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21985

AN:

67966

Other (OTH)

AF:

0.315

AC:

666

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1767

3534

5301

7068

8835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.324

Hom.:

10345

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

(source)

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

PhyloP100

0.84

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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rs12146493

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over