Genetic Variant APOBEC3G:p.His186Arg (chr22-39081561-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021822.4(APOBEC3G):c.557A>G(p.His186Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 1,613,634 control chromosomes in the GnomAD database, including 6,421 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.13 ( 3010 hom., cov: 32)

Exomes 𝑓: 0.040 ( 3411 hom. )

Consequence

APOBEC3G
NM_021822.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Publications

79 publications found

Variant links:

Genes affected

APOBEC3G (HGNC:17357): (apolipoprotein B mRNA editing enzyme catalytic subunit 3G) 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. The protein encoded by this gene catalyzes site-specific deamination of both RNA and single-stranded DNA. The encoded protein has been found to be a specific inhibitor of human immunodeficiency virus-1 (HIV-1) infectivity. [provided by RefSeq, Mar 2017]

APOBEC3G links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=2.7883053E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3G	NM_021822.4 link	c.557A>G	p.His186Arg	missense_variant	Exon 4 of 8	ENST00000407997.4	NP_068594.1	Q9HC16-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4 link	c.557A>G	p.His186Arg	missense_variant	Exon 4 of 8	1	NM_021822.4	ENSP00000385057.3		Q9HC16-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19782

AN:

152062

Hom.:

3008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0716

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.0850

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0515

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0288

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.0594

AC:

14941

AN:

251380

AF XY:

0.0503

show subpopulations

Gnomad AFR exome

AF:

0.373

Gnomad AMR exome

AF:

0.0562

Gnomad ASJ exome

AF:

0.0475

Gnomad EAS exome

AF:

0.0767

Gnomad FIN exome

AF:

0.0534

Gnomad NFE exome

AF:

0.0286

Gnomad OTH exome

AF:

0.0452

GnomAD4 exome

AF:

0.0404

AC:

58970

AN:

1461454

Hom.:

3411

Cov.:

AF XY:

0.0383

AC XY:

27862

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.380

AC:

12701

AN:

33448

American (AMR)

AF:

0.0610

AC:

2727

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

1256

AN:

26124

East Asian (EAS)

AF:

0.0776

AC:

3080

AN:

39694

South Asian (SAS)

AF:

0.0130

AC:

1122

AN:

86252

European-Finnish (FIN)

AF:

0.0488

AC:

2607

AN:

53382

Middle Eastern (MID)

AF:

0.0515

AC:

297

AN:

5764

European-Non Finnish (NFE)

AF:

0.0286

AC:

31769

AN:

1111722

Other (OTH)

AF:

0.0565

AC:

3411

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

2537

5074

7611

10148

12685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.130

AC:

19802

AN:

152180

Hom.:

3010

Cov.:

AF XY:

0.126

AC XY:

9406

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.369

AC:

15303

AN:

41476

American (AMR)

AF:

0.0714

AC:

1092

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

158

AN:

3470

East Asian (EAS)

AF:

0.0852

AC:

441

AN:

5176

South Asian (SAS)

AF:

0.0126

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0515

AC:

546

AN:

10606

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0288

AC:

1959

AN:

68014

Other (OTH)

AF:

0.105

AC:

222

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

720

1439

2159

2878

3598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0573

Hom.:

3335

Bravo

AF:

0.143

TwinsUK

AF:

0.0324

AC:

120

ALSPAC

AF:

0.0314

AC:

121

ESP6500AA

AF:

0.367

AC:

1619

ESP6500EA

AF:

0.0291

AC:

250

ExAC

AF:

0.0639

AC:

7763

Asia WGS

AF:

0.0670

AC:

231

AN:

3478

EpiCase

AF:

0.0301

EpiControl

AF:

0.0298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0030

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.0080

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.63

MetaRNN

Benign

0.00028

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.76

PhyloP100

-1.4

PROVEAN

Benign

-2.2

REVEL

Benign

0.040

Sift

Benign

0.34

Sift4G

Benign

0.96

Polyphen

0.0020

Vest4

0.016

MPC

0.22

ClinPred

0.0086

GERP RS

-2.8

Varity_R

0.10

gMVP

0.31

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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22-39081561-A-G

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