6-41061603-T-C

Variant names:

• chr6-41061603-T-C
• rs2076472
• NM_006789.4:c.407T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 33 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 (MetaRNN=0.0040377676).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 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.407T>C	p.Ile136Thr	missense	Exon 2 of 3	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.407T>C	p.Ile136Thr	missense	Exon 2 of 3	ENSP00000244669.2	Q9Y235
	APOBEC2	ENST00000899065.1		c.407T>C	p.Ile136Thr	missense	Exon 2 of 2	ENSP00000569124.1
	OARD1	ENST00000482853.5	TSL:2	n.144+8473A>G		intron	N/A	ENSP00000420472.1	H7C5Q1

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

GnomAD2 exomes AF: 0.215 AC: 53970 AN: 251208 AF XY: 0.215

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 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

African (AFR) AF: 0.0330 AC: 1104 AN: 33480

American (AMR) AF: 0.296 AC: 13234 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3137 AN: 26136

East Asian (EAS) AF: 0.248 AC: 9838 AN: 39700

South Asian (SAS) AF: 0.273 AC: 23581 AN: 86256

European-Finnish (FIN) AF: 0.219 AC: 11711 AN: 53420

Middle Eastern (MID) AF: 0.151 AC: 869 AN: 5768

European-Non Finnish (NFE) AF: 0.203 AC: 225559 AN: 1112012

Other (OTH) AF: 0.192 AC: 11612 AN: 60396

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

African (AFR) AF: 0.0388 AC: 1611 AN: 41568

American (AMR) AF: 0.234 AC: 3573 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3472

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5178

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4824

European-Finnish (FIN) AF: 0.220 AC: 2323 AN: 10582

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13875 AN: 68012

Other (OTH) AF: 0.149 AC: 315 AN: 2116

Alfa AF: 0.186 Hom.: 9717

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 v4.9

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
PhyloP100		0.28
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
Mutation Taster		=82/18	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: rs2076472; hg19: chr6-41029342; COSMIC: COSV55142006; COSMIC: COSV55142006;