rs11545130

Positions:

• chr22-39087097-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_021822.4(APOBEC3G):​c.1111C>T​(p.Leu371Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,613,962 control chromosomes in the GnomAD database, including 31 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 0.0081 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (17 hom.)
• Consequence: APOBEC3G NM_021822.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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=-0.98).
• BP7: Synonymous conserved (PhyloP=-0.267 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00811 (1235/152294) while in subpopulation AFR AF= 0.0278 (1155/41564). AF 95% confidence interval is 0.0265. There are 14 homozygotes in gnomad4. There are 575 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.1111C>T	p.Leu371Leu	synonymous_variant	7/8	ENST00000407997.4	NP_068594.1
APOBEC3G	NM_001349436.1	c.1078C>T	p.Leu360Leu	synonymous_variant	7/8		NP_001336365.1
APOBEC3G	NM_001349437.2	c.910C>T	p.Leu304Leu	synonymous_variant	6/7		NP_001336366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.1111C>T	p.Leu371Leu	synonymous_variant	7/8	1	NM_021822.4	ENSP00000385057.3

Frequencies

GnomAD3 genomes AF: 0.00808 AC: 1229 AN: 152176 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00214 AC: 537 AN: 251388 Hom.: 4 AF XY: 0.00157 AC XY: 213 AN XY: 135876

Gnomad AFR exome AF: 0.0287

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00100 AC: 1466 AN: 1461668 Hom.: 17 Cov.: 32 AF XY: 0.000876 AC XY: 637 AN XY: 727104

Gnomad4 AFR exome AF: 0.0309

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000200

Gnomad4 OTH exome AF: 0.00194

GnomAD4 genome AF: 0.00811 AC: 1235 AN: 152294 Hom.: 14 Cov.: 32 AF XY: 0.00772 AC XY: 575 AN XY: 74472

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00233 Hom.: 4

Bravo AF: 0.00922

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11545130; hg19: chr22-39483102;