rs12628403

Variant names:

• chr22-38962032-A-C
• rs12628403
• NM_145699.4:c.470-66A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 publications found

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]

ENSG00000305420 (HGNC:):

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 = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3A	NM_145699.4	c.470-66A>C		intron_variant	Intron 3 of 4	ENST00000249116.7	NP_663745.1
APOBEC3A	NM_001270406.2	c.416-66A>C		intron_variant	Intron 3 of 4		NP_001257335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3A	ENST00000249116.7	c.470-66A>C		intron_variant	Intron 3 of 4	1	NM_145699.4	ENSP00000249116.2
APOBEC3A	ENST00000402255.5	c.470-66A>C		intron_variant	Intron 4 of 5	5		ENSP00000384359.1
ENSG00000305420	ENST00000810842.1	n.627-359T>G		intron_variant	Intron 3 of 3

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

African (AFR) AF: 0.0171 AC: 550 AN: 32188

American (AMR) AF: 0.247 AC: 9869 AN: 39914

Ashkenazi Jewish (ASJ) AF: 0.0544 AC: 1228 AN: 22564

East Asian (EAS) AF: 0.314 AC: 12209 AN: 38942

South Asian (SAS) AF: 0.143 AC: 11085 AN: 77624

European-Finnish (FIN) AF: 0.100 AC: 5130 AN: 51130

Middle Eastern (MID) AF: 0.0833 AC: 334 AN: 4012

European-Non Finnish (NFE) AF: 0.0796 AC: 85876 AN: 1079012

Other (OTH) AF: 0.106 AC: 6151 AN: 57756

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

African (AFR) AF: 0.0234 AC: 969 AN: 41372

American (AMR) AF: 0.173 AC: 2640 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3472

East Asian (EAS) AF: 0.342 AC: 1763 AN: 5158

South Asian (SAS) AF: 0.162 AC: 783 AN: 4822

European-Finnish (FIN) AF: 0.0933 AC: 990 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0764 AC: 5190 AN: 67950

Other (OTH) AF: 0.114 AC: 242 AN: 2114

Alfa AF: 0.0842 Hom.: 1499

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
PhyloP100		0.12
Mutation Taster		=100/0	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: rs12628403; hg19: chr22-39358037; COSMIC: COSV50779190; COSMIC: COSV50779190;