rs17496046

Positions:

• chr22-39086366-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000407997.4(APOBEC3G):​c.823C>G​(p.Gln275Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 1,613,934 control chromosomes in the GnomAD database, including 4,282 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.082 (605 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3677 hom.)
• Consequence: APOBEC3G ENST00000407997.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019907653).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.823C>G	p.Gln275Glu	missense_variant	6/8	ENST00000407997.4	NP_068594.1
APOBEC3G	NM_001349436.1	c.790C>G	p.Gln264Glu	missense_variant	6/8		NP_001336365.1
APOBEC3G	NM_001349437.2	c.622C>G	p.Gln208Glu	missense_variant	5/7		NP_001336366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.823C>G	p.Gln275Glu	missense_variant	6/8	1	NM_021822.4	ENSP00000385057	P1

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12497 AN: 152100 Hom.: 604 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0850

GnomAD3 exomes AF: 0.0562 AC: 14121 AN: 251392 Hom.: 510 AF XY: 0.0533 AC XY: 7240 AN XY: 135874

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.0769

Gnomad EAS exome AF: 0.0175

Gnomad SAS exome AF: 0.0156

Gnomad FIN exome AF: 0.0412

Gnomad NFE exome AF: 0.0682

Gnomad OTH exome AF: 0.0641

GnomAD4 exome AF: 0.0661 AC: 96665 AN: 1461716 Hom.: 3677 Cov.: 34 AF XY: 0.0642 AC XY: 46713 AN XY: 727160

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0400

Gnomad4 ASJ exome AF: 0.0806

Gnomad4 EAS exome AF: 0.0242

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.0446

Gnomad4 NFE exome AF: 0.0711

Gnomad4 OTH exome AF: 0.0665

GnomAD4 genome AF: 0.0822 AC: 12513 AN: 152218 Hom.: 605 Cov.: 32 AF XY: 0.0793 AC XY: 5900 AN XY: 74436

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.0202

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0425

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.0846

Alfa AF: 0.0719 Hom.: 292

Bravo AF: 0.0875

TwinsUK AF: 0.0820 AC: 304

ALSPAC AF: 0.0698 AC: 269

ESP6500AA AF: 0.131 AC: 578

ESP6500EA AF: 0.0734 AC: 631

ExAC AF: 0.0573 AC: 6961

Asia WGS AF: 0.0310 AC: 107 AN: 3478

EpiCase AF: 0.0680

EpiControl AF: 0.0649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.2
DANN	Benign	0.72
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	P;P
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.082
Sift	Benign	0.21	T
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.038
MPC		0.75
ClinPred		0.011	T
GERP RS		0.43
Varity_R		0.39
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs17496046; hg19: chr22-39482371; COSMIC: COSV68470264; COSMIC: COSV68470264;