6-41061791-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBEC2	NM_006789.4	c.595T>C	p.Ser199Pro	missense_variant	2/3	ENST00000244669.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBEC2	ENST00000244669.3	c.595T>C	p.Ser199Pro	missense_variant	2/3	1	NM_006789.4	P1
OARD1	ENST00000482853.5	c.145+8285A>G		intron_variant, NMD_transcript_variant		2

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

GnomAD3 exomes AF: 0.00561 AC: 1410 AN: 251418 Hom.: 52 AF XY: 0.00436 AC XY: 592 AN XY: 135894

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 SAS exome AF: 0.000196

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

Gnomad4 AFR exome AF: 0.0740

Gnomad4 AMR exome AF: 0.00478

Gnomad4 ASJ exome AF: 0.000918

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000560

Gnomad4 OTH exome AF: 0.00568

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

Gnomad4 AFR AF: 0.0690

Gnomad4 AMR AF: 0.00955

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00388 Hom.: 22

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	0.61	D
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

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: rs114127156; hg19: chr6-41029530;