22-39081386-T-C

Position:

• chr22-39081386-T-C

Variant summary

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

The NM_021822.4(APOBEC3G):​c.467-85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0491 in 1,531,826 control chromosomes in the GnomAD database, including 6,158 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 0.13 (2992 hom., cov: 32)
  • Exomes 𝑓: 0.040 (3166 hom.)
• Consequence: APOBEC3G NM_021822.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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 (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.467-85T>C		intron_variant		ENST00000407997.4	NP_068594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.467-85T>C		intron_variant		1	NM_021822.4	ENSP00000385057.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19738 AN: 152030 Hom.: 2990 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0401 AC: 55380 AN: 1379678 Hom.: 3166 Cov.: 23 AF XY: 0.0381 AC XY: 26238 AN XY: 688462

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.0617

Gnomad4 ASJ exome AF: 0.0477

Gnomad4 EAS exome AF: 0.0775

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.0481

Gnomad4 NFE exome AF: 0.0284

Gnomad4 OTH exome AF: 0.0561

GnomAD4 genome AF: 0.130 AC: 19757 AN: 152148 Hom.: 2992 Cov.: 32 AF XY: 0.126 AC XY: 9395 AN XY: 74390

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.0717

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.0858

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0288

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0443 Hom.: 757

Bravo AF: 0.143

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.59
DANN	Benign	0.49

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: rs3736685; hg19: chr22-39477391; COSMIC: COSV68470346; COSMIC: COSV68470346;