rs5757465

chr22-39081118-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021822.4(APOBEC3G):c.357T>C(p.Phe119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,614,034 control chromosomes in the GnomAD database, including 136,188 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 0.31 (9178 hom., cov: 32)
  • Exomes 𝑓: 0.41 (127010 hom.)
• Consequence: APOBEC3G NM_021822.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-2.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBEC3G	NM_021822.4	c.357T>C	p.Phe119=	synonymous_variant	3/8	ENST00000407997.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.357T>C	p.Phe119=	synonymous_variant	3/8	1	NM_021822.4	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47743 AN: 152058 Hom.: 9181 Cov.: 32

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.374 AC: 93928 AN: 251462 Hom.: 18886 AF XY: 0.386 AC XY: 52440 AN XY: 135904

Gnomad AFR exome AF: 0.0740

Gnomad AMR exome AF: 0.383

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.228

Gnomad SAS exome AF: 0.434

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.410 AC: 599417 AN: 1461858 Hom.: 127010 Cov.: 72 AF XY: 0.412 AC XY: 299924 AN XY: 727234

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.433

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.314 AC: 47720 AN: 152176 Hom.: 9178 Cov.: 32 AF XY: 0.312 AC XY: 23211 AN XY: 74394

Gnomad4 AFR AF: 0.0842

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.376

Alfa AF: 0.409 Hom.: 26760

Bravo AF: 0.310

Asia WGS AF: 0.301 AC: 1047 AN: 3478

EpiCase AF: 0.444

EpiControl AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.8
Dann	Benign	0.51

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: rs5757465; hg19: chr22-39477123; COSMIC: COSV68470125; COSMIC: COSV68470125;