dbSNP rs610037: AP5B1:p.Leu369Leu (chr11-65779386-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_138368.5(AP5B1):c.1107T>G(p.Leu369Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,598,098 control chromosomes in the GnomAD database, including 217,303 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 0.52 ( 21108 hom., cov: 33)

Exomes 𝑓: 0.51 ( 196195 hom. )

Consequence

AP5B1
NM_138368.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.317

Publications

35 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=0.317 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP5B1	NM_138368.5 link	c.1107T>G	p.Leu369Leu	synonymous_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.1107T>G	p.Leu369Leu	synonymous_variant	Exon 2 of 2	1	NM_138368.5	ENSP00000454303.1		Q2VPB7

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78784

AN:

151992

Hom.:

21079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.355

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.522

GnomAD2 exomes

AF:

0.454

AC:

105404

AN:

232126

AF XY:

0.452

show subpopulations

Gnomad AFR exome

AF:

0.612

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.494

GnomAD4 exome

AF:

0.514

AC:

743709

AN:

1445986

Hom.:

196195

Cov.:

AF XY:

0.508

AC XY:

364462

AN XY:

717710

show subpopulations

African (AFR)

AF:

0.615

AC:

20452

AN:

33260

American (AMR)

AF:

0.353

AC:

15235

AN:

43162

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

10860

AN:

25382

East Asian (EAS)

AF:

0.361

AC:

14213

AN:

39410

South Asian (SAS)

AF:

0.297

AC:

25146

AN:

84664

European-Finnish (FIN)

AF:

0.431

AC:

22249

AN:

51634

Middle Eastern (MID)

AF:

0.505

AC:

2878

AN:

5698

European-Non Finnish (NFE)

AF:

0.546

AC:

601752

AN:

1103066

Other (OTH)

AF:

0.518

AC:

30924

AN:

59710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

23051

46102

69153

92204

115255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16970

33940

50910

67880

84850

<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:

0.518

AC:

78857

AN:

152112

Hom.:

21108

Cov.:

AF XY:

0.505

AC XY:

37537

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.612

AC:

25384

AN:

41490

American (AMR)

AF:

0.434

AC:

6629

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1493

AN:

3472

East Asian (EAS)

AF:

0.355

AC:

1831

AN:

5154

South Asian (SAS)

AF:

0.304

AC:

1468

AN:

4826

European-Finnish (FIN)

AF:

0.393

AC:

4168

AN:

10596

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.531

AC:

36120

AN:

67974

Other (OTH)

AF:

0.519

AC:

1094

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1984

3969

5953

7938

9922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.518

Hom.:

52933

Bravo

AF:

0.529

Asia WGS

AF:

0.397

AC:

1381

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.32

Mutation Taster

=100/0

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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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