Genetic Variant NM_021822.4:c.467-99C>G (chr22-39081372-C-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.467-99C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 1,528,160 control chromosomes in the GnomAD database, including 6,185 homozygotes. In-silico tool predicts 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 ( 2992 hom., cov: 32)

Exomes 𝑓: 0.040 ( 3193 hom. )

Consequence

APOBEC3G
NM_021822.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.972

Publications

7 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 (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021822.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOBEC3G	NM_021822.4	MANE Select	c.467-99C>G	intron	N/A	NP_068594.1	Q9HC16-1
APOBEC3G	NM_001349436.1		c.434-99C>G	intron	N/A	NP_001336365.1
APOBEC3G	NM_001349437.2		c.266-99C>G	intron	N/A	NP_001336366.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOBEC3G	ENST00000407997.4	TSL:1 MANE Select	c.467-99C>G	intron	N/A	ENSP00000385057.3	Q9HC16-1
APOBEC3G	ENST00000960612.1		c.467-99C>G	intron	N/A	ENSP00000630671.1
APOBEC3G	ENST00000851527.1		c.171+2287C>G	intron	N/A	ENSP00000521586.1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19735

AN:

152082

Hom.:

2990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0718

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.0859

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0515

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.0404

AC:

55580

AN:

1375960

Hom.:

3193

Cov.:

AF XY:

0.0384

AC XY:

26290

AN XY:

685138

show subpopulations

African (AFR)

AF:

0.378

AC:

11936

AN:

31584

American (AMR)

AF:

0.0622

AC:

2583

AN:

41526

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

1114

AN:

23176

East Asian (EAS)

AF:

0.0776

AC:

3051

AN:

39302

South Asian (SAS)

AF:

0.0131

AC:

1027

AN:

78696

European-Finnish (FIN)

AF:

0.0477

AC:

2282

AN:

47874

Middle Eastern (MID)

AF:

0.0508

AC:

272

AN:

5356

European-Non Finnish (NFE)

AF:

0.0286

AC:

30089

AN:

1051230

Other (OTH)

AF:

0.0564

AC:

3226

AN:

57216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2598

5195

7793

10390

12988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1336

2672

4008

5344

6680

<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:

0.130

AC:

19755

AN:

152200

Hom.:

2992

Cov.:

AF XY:

0.126

AC XY:

9395

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.368

AC:

15252

AN:

41470

American (AMR)

AF:

0.0716

AC:

1095

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

158

AN:

3472

East Asian (EAS)

AF:

0.0861

AC:

446

AN:

5182

South Asian (SAS)

AF:

0.0126

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0515

AC:

547

AN:

10614

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0287

AC:

1955

AN:

68014

Other (OTH)

AF:

0.105

AC:

221

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

696

1392

2088

2784

3480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0803

Hom.:

232

Bravo

AF:

0.143

Asia WGS

AF:

0.0660

AC:

230

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.66

(source)

DANN

Benign

0.38

PhyloP100

-0.97

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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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