chr6-41054211-C-G

Variant names:

• chr6-41054211-C-G
• rs2268196
• NM_006789.4:c.131+733C>G

Variant summary

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

The NM_006789.4(APOBEC2):​c.131+733C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,104 control chromosomes in the GnomAD database, including 12,168 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 0.39 (12168 hom., cov: 33)
• Consequence: APOBEC2 NM_006789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC2	NM_006789.4	c.131+733C>G		intron_variant	Intron 1 of 2	ENST00000244669.3	NP_006780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC2	ENST00000244669.3	c.131+733C>G		intron_variant	Intron 1 of 2	1	NM_006789.4	ENSP00000244669.2
OARD1	ENST00000482853.5	n.145-1848G>C		intron_variant	Intron 2 of 4	2		ENSP00000420472.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59123 AN: 151986 Hom.: 12159 Cov.: 33

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.389 AC: 59175 AN: 152104 Hom.: 12168 Cov.: 33 AF XY: 0.384 AC XY: 28588 AN XY: 74366

African (AFR) AF: 0.515 AC: 21362 AN: 41476

American (AMR) AF: 0.402 AC: 6144 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5168

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4828

European-Finnish (FIN) AF: 0.313 AC: 3312 AN: 10582

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23139 AN: 67978

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.379 Hom.: 1435

Bravo AF: 0.401

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.56
PhyloP100		0.26
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: rs2268196; hg19: chr6-41021950;