22-39077041-C-G

Variant names:

• chr22-39077041-C-G
• rs5750743
• NM_001349436.1:c.-144C>G

Variant summary

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

The NM_001349436.1(APOBEC3G):​c.-144C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.53 (12947 hom., cov: 28)
  • Exomes 𝑓: 0.65 (72107 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOBEC3G NM_001349436.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 6 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=-0.89).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3G	NM_021822.4	c.-321C>G		upstream_gene_variant		ENST00000407997.4	NP_068594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3G	ENST00000407997.4	c.-321C>G		upstream_gene_variant		1	NM_021822.4	ENSP00000385057.3
APOBEC3G	ENST00000461827.5	n.-43C>G		upstream_gene_variant		3
APOBEC3G	ENST00000463934.1	n.-26C>G		upstream_gene_variant		2
APOBEC3G	ENST00000480000.5	n.-38C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.532 AC: 73099 AN: 137346 Hom.: 12946 Cov.: 28

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.654 AC: 219264 AN: 335120 Hom.: 72107 Cov.: 3 AF XY: 0.650 AC XY: 114338 AN XY: 175920

African (AFR) AF: 0.664 AC: 6690 AN: 10070

American (AMR) AF: 0.741 AC: 10745 AN: 14504

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 6735 AN: 10352

East Asian (EAS) AF: 0.752 AC: 16511 AN: 21960

South Asian (SAS) AF: 0.595 AC: 22285 AN: 37444

European-Finnish (FIN) AF: 0.555 AC: 10887 AN: 19632

Middle Eastern (MID) AF: 0.652 AC: 950 AN: 1456

European-Non Finnish (NFE) AF: 0.657 AC: 131464 AN: 200212

Other (OTH) AF: 0.667 AC: 12997 AN: 19490

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.532 AC: 73142 AN: 137456 Hom.: 12947 Cov.: 28 AF XY: 0.525 AC XY: 35215 AN XY: 67064

African (AFR) AF: 0.547 AC: 20188 AN: 36906

American (AMR) AF: 0.579 AC: 7810 AN: 13480

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1675 AN: 3190

East Asian (EAS) AF: 0.599 AC: 2777 AN: 4634

South Asian (SAS) AF: 0.494 AC: 2188 AN: 4432

European-Finnish (FIN) AF: 0.478 AC: 4702 AN: 9840

Middle Eastern (MID) AF: 0.622 AC: 173 AN: 278

European-Non Finnish (NFE) AF: 0.519 AC: 32159 AN: 61928

Other (OTH) AF: 0.561 AC: 1081 AN: 1928

Alfa AF: 0.424 Hom.: 539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		0.040
PromoterAI		-0.43	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5750743; hg19: chr22-39473046;