6-41061791-T-C

Variant names:

• chr6-41061791-T-C
• rs114127156
• NM_006789.4:c.595T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006789.4(APOBEC2):​c.595T>C​(p.Ser199Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,614,136 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (96 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (110 hom.)
• Consequence: APOBEC2 NM_006789.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017673075).
• BP6: Variant 6-41061791-T-C is Benign according to our data. Variant chr6-41061791-T-C is described in ClinVar as Benign. ClinVar VariationId is 783754.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0669 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.595T>C	p.Ser199Pro	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.595T>C	p.Ser199Pro	missense	Exon 2 of 3	ENSP00000244669.2	Q9Y235
	APOBEC2	ENST00000899065.1		c.595T>C	p.Ser199Pro	missense	Exon 2 of 2	ENSP00000569124.1
	OARD1	ENST00000482853.5	TSL:2	n.144+8285A>G		intron	N/A	ENSP00000420472.1	H7C5Q1

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3085 AN: 152126 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00561 AC: 1410 AN: 251418 AF XY: 0.00436

Gnomad AFR exome AF: 0.0732

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000563

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00257 AC: 3757 AN: 1461892 Hom.: 110 Cov.: 32 AF XY: 0.00232 AC XY: 1687 AN XY: 727246

African (AFR) AF: 0.0740 AC: 2476 AN: 33480

American (AMR) AF: 0.00478 AC: 214 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000918 AC: 24 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.000560 AC: 623 AN: 1112012

Other (OTH) AF: 0.00568 AC: 343 AN: 60394

GnomAD4 genome AF: 0.0203 AC: 3088 AN: 152244 Hom.: 96 Cov.: 32 AF XY: 0.0201 AC XY: 1496 AN XY: 74434

African (AFR) AF: 0.0690 AC: 2866 AN: 41540

American (AMR) AF: 0.00955 AC: 146 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68016

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.00798 Hom.: 86

Bravo AF: 0.0233

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0695 AC: 306

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00698 AC: 847

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.070
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.18
MVP		0.64
MPC		0.070
ClinPred		0.016	T
GERP RS		3.3
Varity_R		0.43
gMVP		0.45
Mutation Taster		=95/5	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: rs114127156; hg19: chr6-41029530;