Genetic Variant APOBEC3B:p.Pro8Leu (chr22-38984080-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004900.5(APOBEC3B):c.23C>T(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,575,790 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000055 ( 7 hom. )

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.311

Publications

0 publications found

Variant links:

Genes affected

APOBEC3B (HGNC:17352): (apolipoprotein B mRNA editing enzyme catalytic subunit 3B) This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. It is thought that the proteins may be RNA editing enzymes and have roles in growth or cell cycle control. A hybrid gene results from the deletion of approximately 29.5 kb of sequence between this gene, APOBEC3B, and the adjacent gene APOBEC3A. The breakpoints of the deletion are within the two genes, so the deletion allele is predicted to have the promoter and coding region of APOBEC3A, but the 3' UTR of APOBEC3B. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

APOBEC3B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12114337).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004900.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3B	NM_004900.5	MANE Select	c.23C>T	p.Pro8Leu	missense	Exon 2 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.23C>T	p.Pro8Leu	missense	Exon 2 of 8	NP_001257340.2	Q9UH17-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOBEC3B	ENST00000333467.4	TSL:1 MANE Select	c.23C>T	p.Pro8Leu	missense	Exon 2 of 8	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7	TSL:1	c.23C>T	p.Pro8Leu	missense	Exon 2 of 8	ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9	TSL:1	n.23C>T		non_coding_transcript_exon	Exon 2 of 7	ENSP00000338897.5	Q9UH17-2

Frequencies

GnomAD3 genomes

AF:

0.0000403

AC:

AN:

148754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000967

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000742

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000393

AC:

AN:

228892

AF XY:

0.0000161

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000465

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1427036

Hom.:

Cov.:

AF XY:

0.0000522

AC XY:

AN XY:

709190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32886

American (AMR)

AF:

0.0000784

AC:

AN:

38262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25116

East Asian (EAS)

AF:

0.0000847

AC:

AN:

35434

South Asian (SAS)

AF:

0.0000370

AC:

AN:

81072

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4242

European-Non Finnish (NFE)

AF:

0.0000600

AC:

AN:

1099112

Other (OTH)

AF:

0.0000511

AC:

AN:

58652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000403

AC:

AN:

148754

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40876

American (AMR)

AF:

0.00

AC:

AN:

14498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

4450

South Asian (SAS)

AF:

0.00

AC:

AN:

4532

European-Finnish (FIN)

AF:

0.0000967

AC:

AN:

10346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000742

AC:

AN:

67394

Other (OTH)

AF:

0.00

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

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:

0.0000369

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000251

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.055

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.72

M_CAP

Benign

0.079

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PhyloP100

-0.31

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.073

Sift

Benign

0.052

Sift4G

Benign

0.11

Polyphen

0.86

Vest4

0.14

MVP

0.62

MPC

1.4

ClinPred

0.15

GERP RS

-3.2

Varity_R

0.13

gMVP

0.70

Mutation Taster

=100/0

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