6-41061603-T-C

Position:

• chr6-41061603-T-C

Variant summary

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

The NM_006789.4(APOBEC2):​c.407T>C​(p.Ile136Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,614,142 control chromosomes in the GnomAD database, including 34,805 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2624 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32181 hom.)
• Consequence: APOBEC2 NM_006789.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040377676).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC2	NM_006789.4	c.407T>C	p.Ile136Thr	missense_variant	2/3	ENST00000244669.3	NP_006780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC2	ENST00000244669.3	c.407T>C	p.Ile136Thr	missense_variant	2/3	1	NM_006789.4	ENSP00000244669.2
OARD1	ENST00000482853.5	n.144+8473A>G		intron_variant		2		ENSP00000420472.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24945 AN: 152132 Hom.: 2620 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.215 AC: 53970 AN: 251208 Hom.: 6537 AF XY: 0.215 AC XY: 29201 AN XY: 135768

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.250

Gnomad SAS exome AF: 0.278

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.206 AC: 300645 AN: 1461892 Hom.: 32181 Cov.: 34 AF XY: 0.207 AC XY: 150677 AN XY: 727246

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.164 AC: 24952 AN: 152250 Hom.: 2624 Cov.: 32 AF XY: 0.167 AC XY: 12424 AN XY: 74432

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.149

Alfa AF: 0.191 Hom.: 7395

Bravo AF: 0.157

TwinsUK AF: 0.202 AC: 749

ALSPAC AF: 0.194 AC: 747

ESP6500AA AF: 0.0404 AC: 178

ESP6500EA AF: 0.203 AC: 1747

ExAC AF: 0.210 AC: 25558

Asia WGS AF: 0.281 AC: 975 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.76
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.050	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.025
Sift	Benign	0.083	T
Sift4G	Benign	0.092	T
Polyphen		0.0	B
Vest4		0.034
MPC		0.070
ClinPred		0.00052	T
GERP RS		1.4
Varity_R		0.14
gMVP		0.40

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: rs2076472; hg19: chr6-41029342; COSMIC: COSV55142006; COSMIC: COSV55142006;