rs5757402

Variant names:

• chr22-38954067-T-C
• rs5757402
• ENST00000402255.5:c.-105+1217T>C

Variant summary

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

The ENST00000402255.5(APOBEC3A):​c.-105+1217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,036 control chromosomes in the GnomAD database, including 35,548 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 0.68 (35548 hom., cov: 32)
• Consequence: APOBEC3A ENST00000402255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 2 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]

ENSG00000305435 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3A	ENST00000402255.5	c.-105+1217T>C		intron_variant	Intron 1 of 5	5		ENSP00000384359.1
ENSG00000305435	ENST00000810903.1	n.-4A>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102992 AN: 151918 Hom.: 35476 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.630

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.678 AC: 103130 AN: 152036 Hom.: 35548 Cov.: 32 AF XY: 0.684 AC XY: 50805 AN XY: 74314

African (AFR) AF: 0.764 AC: 31658 AN: 41434

American (AMR) AF: 0.676 AC: 10324 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3468

East Asian (EAS) AF: 0.945 AC: 4898 AN: 5184

South Asian (SAS) AF: 0.814 AC: 3928 AN: 4826

European-Finnish (FIN) AF: 0.630 AC: 6658 AN: 10576

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41725 AN: 67952

Other (OTH) AF: 0.636 AC: 1344 AN: 2114

Alfa AF: 0.639 Hom.: 57249

Bravo AF: 0.683

Asia WGS AF: 0.853 AC: 2967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.64
PhyloP100		-0.54
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: rs5757402; hg19: chr22-39350072;