rs17000697

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004900.5(APOBEC3B):c.325T>G(p.Ser109Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,599,074 control chromosomes in the GnomAD database, including 447 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 35 hom., cov: 28)

Exomes 𝑓: 0.0053 ( 412 hom. )

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.03

Publications

10 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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006128192).

BP6

Variant 22-38985962-T-G is Benign according to our data. Variant chr22-38985962-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2653140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 35 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3B	NM_004900.5	MANE Select	c.325T>G	p.Ser109Ala	missense	Exon 3 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.325T>G	p.Ser109Ala	missense	Exon 3 of 8	NP_001257340.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
APOBEC3B	ENST00000333467.4	TSL:1 MANE Select	c.325T>G	p.Ser109Ala	missense	Exon 3 of 8	ENSP00000327459.3
APOBEC3B	ENST00000407298.7	TSL:1	c.325T>G	p.Ser109Ala	missense	Exon 3 of 8	ENSP00000385068.3
APOBEC3B	ENST00000335760.9	TSL:1	n.325T>G		non_coding_transcript_exon	Exon 3 of 7	ENSP00000338897.5

Frequencies

GnomAD3 genomes

AF:

0.00463

AC:

684

AN:

147604

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00429

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000579

Gnomad EAS

AF:

0.000692

Gnomad SAS

AF:

0.00317

Gnomad FIN

AF:

0.000777

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00659

Gnomad OTH

AF:

0.00555

GnomAD2 exomes

AF:

0.00302

AC:

752

AN:

248958

AF XY:

0.00329

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.000287

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00438

Gnomad OTH exome

AF:

0.00362

GnomAD4 exome

AF:

0.00526

AC:

7638

AN:

1451398

Hom.:

412

Cov.:

AF XY:

0.00525

AC XY:

3792

AN XY:

721974

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00357

AC:

119

AN:

33326

American (AMR)

AF:

0.00193

AC:

AN:

43978

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26092

East Asian (EAS)

AF:

0.000380

AC:

AN:

36870

South Asian (SAS)

AF:

0.00305

AC:

260

AN:

85228

European-Finnish (FIN)

AF:

0.00190

AC:

101

AN:

53064

Middle Eastern (MID)

AF:

0.000699

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00608

AC:

6735

AN:

1107270

Other (OTH)

AF:

0.00490

AC:

293

AN:

59850

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.370

Heterozygous variant carriers

273

546

820

1093

1366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

240

480

720

960

1200

<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:

0.00465

AC:

686

AN:

147676

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

312

AN XY:

71832

show subpopulations

African (AFR)

AF:

0.00433

AC:

176

AN:

40654

American (AMR)

AF:

0.00209

AC:

AN:

14366

Ashkenazi Jewish (ASJ)

AF:

0.000579

AC:

AN:

3452

East Asian (EAS)

AF:

0.000695

AC:

AN:

4318

South Asian (SAS)

AF:

0.00317

AC:

AN:

4410

European-Finnish (FIN)

AF:

0.000777

AC:

AN:

10290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00659

AC:

442

AN:

67038

Other (OTH)

AF:

0.00556

AC:

AN:

1978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

118

147

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:

0.00513

Hom.:

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00366

AC:

444

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

APOBEC3B-related condition (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.023

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.0011

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.18

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

PhyloP100

-1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

1.4

REVEL

Benign

0.088

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.069

MVP

0.29

MPC

1.1

ClinPred

0.00028

GERP RS

-2.9

Varity_R

0.087

gMVP

0.091

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over