Genetic Variant APOBEC4:p.Lys331Glu (chr1-183647791-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_203454.3(APOBEC4):c.991A>G(p.Lys331Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,613,798 control chromosomes in the GnomAD database, including 126,232 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12181 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114051 hom. )

Consequence

APOBEC4
NM_203454.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0370

Publications

40 publications found

Variant links:

Genes affected

APOBEC4 (HGNC:32152): (apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4) This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008]

APOBEC4 links:

RGL1 (HGNC:30281): (ral guanine nucleotide dissociation stimulator like 1) Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RGL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.220571E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC4	NM_203454.3 link	c.991A>G	p.Lys331Glu	missense_variant	Exon 2 of 2	ENST00000308641.6	NP_982279.1	Q8WW27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOBEC4	ENST00000308641.6 link	c.991A>G	p.Lys331Glu	missense_variant	Exon 2 of 2	1	NM_203454.3	ENSP00000310622.4	Q8WW27
RGL1	ENST00000304685.8 link	c.-33+11290T>C		intron_variant	Intron 1 of 18	1		ENSP00000303192.3	Q9NZL6-2
APOBEC4	ENST00000481562.1 link	n.252A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60265

AN:

151846

Hom.:

12162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.379

GnomAD2 exomes

AF:

0.363

AC:

91341

AN:

251460

AF XY:

0.362

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.302

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.397

Gnomad OTH exome

AF:

0.377

GnomAD4 exome

AF:

0.391

AC:

572250

AN:

1461834

Hom.:

114051

Cov.:

AF XY:

0.389

AC XY:

282902

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.481

AC:

16103

AN:

33478

American (AMR)

AF:

0.304

AC:

13601

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

9586

AN:

26136

East Asian (EAS)

AF:

0.186

AC:

7367

AN:

39700

South Asian (SAS)

AF:

0.329

AC:

28351

AN:

86252

European-Finnish (FIN)

AF:

0.362

AC:

19341

AN:

53414

Middle Eastern (MID)

AF:

0.450

AC:

2592

AN:

5766

European-Non Finnish (NFE)

AF:

0.406

AC:

451572

AN:

1111978

Other (OTH)

AF:

0.393

AC:

23737

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

21095

42191

63286

84382

105477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13984

27968

41952

55936

69920

<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:

0.397

AC:

60324

AN:

151964

Hom.:

12181

Cov.:

AF XY:

0.392

AC XY:

29108

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.470

AC:

19458

AN:

41420

American (AMR)

AF:

0.337

AC:

5143

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1245

AN:

3472

East Asian (EAS)

AF:

0.213

AC:

1104

AN:

5180

South Asian (SAS)

AF:

0.315

AC:

1518

AN:

4818

European-Finnish (FIN)

AF:

0.362

AC:

3824

AN:

10552

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.396

AC:

26870

AN:

67930

Other (OTH)

AF:

0.376

AC:

795

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1863

3725

5588

7450

9313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.393

Hom.:

42729

Bravo

AF:

0.401

TwinsUK

AF:

0.408

AC:

1514

ALSPAC

AF:

0.426

AC:

1643

ESP6500AA

AF:

0.469

AC:

2068

ESP6500EA

AF:

0.395

AC:

3401

ExAC

AF:

0.368

AC:

44672

Asia WGS

AF:

0.274

AC:

955

AN:

3478

EpiCase

AF:

0.397

EpiControl

AF:

0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.18

MetaRNN

Benign

0.00022

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.3

PhyloP100

0.037

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.3

REVEL

Benign

0.046

Sift

Benign

0.74

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.021

MPC

0.15

ClinPred

0.0053

GERP RS

-0.47

Varity_R

0.073

gMVP

0.087

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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