22-39087962-T-C

Variant names:

• chr22-39087962-T-C
• rs5757472
• NM_021822.4:c.*541T>C

Variant summary

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

The NM_021822.4(APOBEC3G):​c.*541T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,776 control chromosomes in the GnomAD database, including 32,977 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 0.66 (32977 hom., cov: 31)
• Consequence: APOBEC3G NM_021822.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• Publications: 3 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.*541T>C		downstream_gene_variant		ENST00000407997.4	NP_068594.1
APOBEC3G	NM_001349436.1	c.*541T>C		downstream_gene_variant			NP_001336365.1
APOBEC3G	NM_001349437.2	c.*541T>C		downstream_gene_variant			NP_001336366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.*541T>C		downstream_gene_variant		1	NM_021822.4	ENSP00000385057.3

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99763 AN: 151660 Hom.: 32962 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.692

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.658 AC: 99822 AN: 151776 Hom.: 32977 Cov.: 31 AF XY: 0.653 AC XY: 48406 AN XY: 74134

African (AFR) AF: 0.666 AC: 27529 AN: 41328

American (AMR) AF: 0.725 AC: 11061 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2292 AN: 3468

East Asian (EAS) AF: 0.753 AC: 3889 AN: 5164

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4812

European-Finnish (FIN) AF: 0.564 AC: 5916 AN: 10488

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44155 AN: 67938

Other (OTH) AF: 0.695 AC: 1467 AN: 2110

Alfa AF: 0.648 Hom.: 3736

Bravo AF: 0.675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.54
PhyloP100		-2.9

Splicing

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

Other links and lift over

dbSNP: rs5757472; hg19: chr22-39483967;