6-41059781-C-T

Variant names:

• chr6-41059781-C-T
• rs2395754
• NM_006789.4:c.132-1547C>T

Variant summary

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

The NM_006789.4(APOBEC2):​c.132-1547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,048 control chromosomes in the GnomAD database, including 24,775 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 0.55 (24775 hom., cov: 31)
• Consequence: APOBEC2 NM_006789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 7 publications found

Genes affected

APOBEC2 (HGNC:605): (apolipoprotein B mRNA editing enzyme catalytic subunit 2) Enables cytidine deaminase activity and identical protein binding activity. Involved in DNA demethylation. Acts upstream of or within cytidine to uridine editing. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

OARD1 (HGNC:21257): (O-acyl-ADP-ribose deacylase 1) The protein encoded by this gene is a deacylase that can convert O-acetyl-ADP-ribose to ADP-ribose and acetate, O-propionyl-ADP-ribose to ADP-ribose and propionate, and O-butyryl-ADP-ribose to ADP-ribose and butyrate. The ADP-ribose product is able to inhibit these reactions through a competitive feedback loop. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006789.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC2	NM_006789.4	MANE Select	c.132-1547C>T		intron	N/A	NP_006780.1	Q9Y235

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC2	ENST00000244669.3	TSL:1 MANE Select	c.132-1547C>T		intron	N/A	ENSP00000244669.2	Q9Y235
	APOBEC2	ENST00000899065.1		c.132-1547C>T		intron	N/A	ENSP00000569124.1
	OARD1	ENST00000482853.5	TSL:2	n.145-7418G>A		intron	N/A	ENSP00000420472.1	H7C5Q1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83628 AN: 151930 Hom.: 24728 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.551 AC: 83731 AN: 152048 Hom.: 24775 Cov.: 31 AF XY: 0.546 AC XY: 40556 AN XY: 74302

African (AFR) AF: 0.783 AC: 32501 AN: 41484

American (AMR) AF: 0.530 AC: 8111 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2069 AN: 5132

South Asian (SAS) AF: 0.511 AC: 2457 AN: 4808

European-Finnish (FIN) AF: 0.402 AC: 4249 AN: 10578

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31058 AN: 67970

Other (OTH) AF: 0.533 AC: 1125 AN: 2110

Alfa AF: 0.487 Hom.: 69462

Bravo AF: 0.569

Asia WGS AF: 0.539 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		-1.1
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: rs2395754; hg19: chr6-41027520;