22-38986390-C-T

Variant names:

Variant summary

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

The NM_004900.5(APOBEC3B):c.547C>T(p.Arg183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,593,644 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000034 ( 1 hom., cov: 30)

Exomes 𝑓: 0.000046 ( 6 hom. )

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.45

Publications

2 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:

Genome browser will be placed here

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=0.079337835).

BS2

High Homozygotes in GnomAdExome4 at 6 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.547C>T	p.Arg183Cys	missense	Exon 4 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.547C>T	p.Arg183Cys	missense	Exon 4 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.547C>T	p.Arg183Cys	missense	Exon 4 of 8	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7	TSL:1	c.547C>T	p.Arg183Cys	missense	Exon 4 of 8	ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9	TSL:1	n.547C>T		non_coding_transcript_exon	Exon 4 of 7	ENSP00000338897.5	Q9UH17-2

Frequencies

GnomAD3 genomes

AF:

0.0000336

AC:

AN:

148850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000688

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:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000735

AC:

AN:

244964

AF XY:

0.000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000620

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000457

AC:

AN:

1444794

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

718820

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33374

American (AMR)

AF:

0.0000477

AC:

AN:

41922

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.0000278

AC:

AN:

35930

South Asian (SAS)

AF:

0.0000831

AC:

AN:

84242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52942

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.0000434

AC:

AN:

1105202

Other (OTH)

AF:

0.0000841

AC:

AN:

59422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.0000336

AC:

AN:

148850

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72418

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

40906

American (AMR)

AF:

0.0000688

AC:

AN:

14538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

4444

South Asian (SAS)

AF:

0.00

AC:

AN:

4556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000446

AC:

AN:

67338

Other (OTH)

AF:

0.00

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0000775

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000667

AC:

EpiCase

AF:

0.000110

EpiControl

AF:

0.000179

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.12

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.021

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.10

M_CAP

Benign

0.026

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-2.4

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.095

Sift

Benign

0.19

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.17

MVP

0.48

MPC

0.51

ClinPred

0.023

GERP RS

-4.3

Varity_R

0.11

gMVP

0.50

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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