chr22-39087827-C-T

Variant names:

• chr22-39087827-C-T
• rs35342554
• NM_021822.4:c.*406C>T

Variant summary

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

The NM_021822.4(APOBEC3G):​c.*406C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 232,664 control chromosomes in the GnomAD database, including 2,107 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 0.090 (2031 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (76 hom.)
• Consequence: APOBEC3G NM_021822.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.*406C>T		downstream_gene_variant		ENST00000407997.4	NP_068594.1
APOBEC3G	NM_001349436.1	c.*406C>T		downstream_gene_variant			NP_001336365.1
APOBEC3G	NM_001349437.2	c.*406C>T		downstream_gene_variant			NP_001336366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.*406C>T		downstream_gene_variant		1	NM_021822.4	ENSP00000385057.3

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13560 AN: 150020 Hom.: 2028 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00360

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000773

Gnomad OTH AF: 0.0658

GnomAD4 exome AF: 0.00811 AC: 669 AN: 82524 Hom.: 76 AF XY: 0.00687 AC XY: 313 AN XY: 45558

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00213

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000692

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0905 AC: 13585 AN: 150140 Hom.: 2031 Cov.: 32 AF XY: 0.0876 AC XY: 6429 AN XY: 73376

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00318

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000773

Gnomad4 OTH AF: 0.0660

Alfa AF: 0.0706 Hom.: 176

Bravo AF: 0.101

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35342554; hg19: chr22-39483832;