rs12628403

Positions:

• chr22-38962032-A-C
• chr22-38962032-A-G

Variant summary

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

The NM_145699.4(APOBEC3A):​c.470-66A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 1,555,134 control chromosomes in the GnomAD database, including 9,457 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 0.085 (942 hom., cov: 31)
  • Exomes 𝑓: 0.094 (8515 hom.)
• Consequence: APOBEC3A NM_145699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

Genes affected

APOBEC3A (HGNC:17343): (apolipoprotein B mRNA editing enzyme catalytic subunit 3A) 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 lacks the zinc binding activity of other family members. The protein plays a role in immunity, by restricting transmission of foreign DNA such as viruses. One mechanism of foreign DNA restriction is deamination of foreign double-stranded DNA cytidines to uridines, which leads to DNA degradation. However, other mechanisms are also thought to be involved, as anti-viral effect is not dependent on deaminase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -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 = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3A	NM_145699.4	c.470-66A>C		intron_variant		ENST00000249116.7	NP_663745.1
APOBEC3A	NM_001270406.2	c.416-66A>C		intron_variant			NP_001257335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3A	ENST00000249116.7	c.470-66A>C		intron_variant		1	NM_145699.4	ENSP00000249116	P1
APOBEC3A	ENST00000402255.5	c.470-66A>C		intron_variant		5		ENSP00000384359	P1

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12876 AN: 151874 Hom.: 920 Cov.: 31

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0944 AC: 132432 AN: 1403142 Hom.: 8515 AF XY: 0.0954 AC XY: 65883 AN XY: 690844

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.0544

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0796

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0850 AC: 12919 AN: 151992 Hom.: 942 Cov.: 31 AF XY: 0.0899 AC XY: 6678 AN XY: 74314

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0933

Gnomad4 NFE AF: 0.0764

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0775 Hom.: 119

Bravo AF: 0.0926

Asia WGS AF: 0.285 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.51

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: rs12628403; hg19: chr22-39358037; COSMIC: COSV50779190; COSMIC: COSV50779190;