22-39087839-C-T

Variant names:

• chr22-39087839-C-T
• rs35228531
• NM_021822.4:c.*418C>T

Variant summary

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

The NM_021822.4(APOBEC3G):​c.*418C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0553 in 227,608 control chromosomes in the GnomAD database, including 1,679 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 0.080 (1628 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (51 hom.)
• Consequence: APOBEC3G NM_021822.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.*418C>T		downstream_gene_variant		ENST00000407997.4	NP_068594.1
APOBEC3G	NM_001349436.1	c.*418C>T		downstream_gene_variant			NP_001336365.1
APOBEC3G	NM_001349437.2	c.*418C>T		downstream_gene_variant			NP_001336366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.*418C>T		downstream_gene_variant		1	NM_021822.4	ENSP00000385057.3

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12079 AN: 151948 Hom.: 1627 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.0566

GnomAD4 exome AF: 0.00635 AC: 480 AN: 75542 Hom.: 51 AF XY: 0.00526 AC XY: 219 AN XY: 41674

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000534

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000629

Gnomad4 OTH exome AF: 0.00748

GnomAD4 genome AF: 0.0796 AC: 12097 AN: 152066 Hom.: 1628 Cov.: 32 AF XY: 0.0770 AC XY: 5728 AN XY: 74356

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.0560

Alfa AF: 0.00131 Hom.: 2

Bravo AF: 0.0896

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35228531; hg19: chr22-39483844;