chr22-39081561-A-G

Position:

• chr22-39081561-A-G

Variant summary

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

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. 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 0.13 (3010 hom., cov: 32)
  • Exomes 𝑓: 0.040 (3411 hom.)
• Consequence: APOBEC3G NM_021822.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.557A>G	p.His186Arg	missense_variant	4/8	ENST00000407997.4	NP_068594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.557A>G	p.His186Arg	missense_variant	4/8	1	NM_021822.4	ENSP00000385057.3

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

GnomAD3 exomes AF: 0.0594 AC: 14941 AN: 251380 Hom.: 1332 AF XY: 0.0503 AC XY: 6836 AN XY: 135874

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 SAS exome AF: 0.0120

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

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.0610

Gnomad4 ASJ exome AF: 0.0481

Gnomad4 EAS exome AF: 0.0776

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.0488

Gnomad4 NFE exome AF: 0.0286

Gnomad4 OTH exome AF: 0.0565

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

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.0714

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0288

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0496 Hom.: 1331

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	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
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

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