22-39081561-A-G

Variant names:

• chr22-39081561-A-G
• rs8177832
• NM_021822.4:c.557A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000407997.4(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 ENST00000407997.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 79 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000407997.4. 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
	APOBEC3G	NM_021822.4	MANE Select	c.557A>G	p.His186Arg	missense	Exon 4 of 8	NP_068594.1
	APOBEC3G	NM_001349436.1		c.524A>G	p.His175Arg	missense	Exon 4 of 8	NP_001336365.1
	APOBEC3G	NM_001349437.2		c.356A>G	p.His119Arg	missense	Exon 3 of 7	NP_001336366.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3G	ENST00000407997.4	TSL:1 MANE Select	c.557A>G	p.His186Arg	missense	Exon 4 of 8	ENSP00000385057.3
	APOBEC3G	ENST00000461827.5	TSL:3	n.625A>G		non_coding_transcript_exon	Exon 4 of 5
	APOBEC3G	ENST00000480000.5	TSL:2	n.686A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19782 AN: 152062 Hom.: 3008 Cov.: 32

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

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.: 31 AF XY: 0.0383 AC XY: 27862 AN XY: 727070

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

GnomAD4 genome AF: 0.130 AC: 19802 AN: 152180 Hom.: 3010 Cov.: 32 AF XY: 0.126 AC XY: 9406 AN XY: 74384

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: 61 AN: 4826

European-Finnish (FIN) AF: 0.0515 AC: 546 AN: 10606

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0288 AC: 1959 AN: 68014

Other (OTH) AF: 0.105 AC: 222 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0030
DANN	Benign	0.14
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.00028	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.76	N
PhyloP100		-1.4
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.040
Sift	Benign	0.34	T
Sift4G	Benign	0.96	T
Polyphen		0.0020	B
Vest4		0.016
MPC		0.22
ClinPred		0.0086	T
GERP RS		-2.8
Varity_R		0.10
gMVP		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8177832; hg19: chr22-39477566; COSMIC: COSV68470127; COSMIC: COSV68470127;