Variant 1-183647749-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_203454.3(APOBEC4):c.1033G>A(p.Val345Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,613,802 control chromosomes in the GnomAD database, including 2,030 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 0.069 ( 626 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1404 hom. )

Consequence

APOBEC4
NM_203454.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.238

Variant links:

Genes affected

APOBEC4 (HGNC:32152): (apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4) This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008]

APOBEC4 links:

RGL1 (HGNC:30281): (ral guanine nucleotide dissociation stimulator like 1) Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RGL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025907457).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBEC4	NM_203454.3 linkuse as main transcript	c.1033G>A	p.Val345Met	missense_variant	2/2	ENST00000308641.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBEC4	ENST00000308641.6 linkuse as main transcript	c.1033G>A	p.Val345Met	missense_variant	2/2	1	NM_203454.3	P1
RGL1	ENST00000304685.8 linkuse as main transcript	c.-33+11248C>T		intron_variant		1			Q9NZL6-2
APOBEC4	ENST00000481562.1 linkuse as main transcript	n.294G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0685

AC:

10417

AN:

152108

Hom.:

620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.0803

Gnomad SAS

AF:

0.0627

Gnomad FIN

AF:

0.0262

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0434

AC:

10896

AN:

251340

Hom.:

425

AF XY:

0.0429

AC XY:

5826

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.0168

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.0830

Gnomad SAS exome

AF:

0.0656

Gnomad FIN exome

AF:

0.0272

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0356

GnomAD4 exome

AF:

0.0348

AC:

50922

AN:

1461576

Hom.:

1404

Cov.:

AF XY:

0.0354

AC XY:

25703

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.0450

Gnomad4 SAS exome

AF:

0.0661

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.0291

Gnomad4 OTH exome

AF:

0.0419

GnomAD4 genome

AF:

0.0686

AC:

10438

AN:

152226

Hom.:

626

Cov.:

AF XY:

0.0675

AC XY:

5022

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.0347

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.0809

Gnomad4 SAS

AF:

0.0629

Gnomad4 FIN

AF:

0.0262

Gnomad4 NFE

AF:

0.0287

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0346

Hom.:

300

Bravo

AF:

0.0732

TwinsUK

AF:

0.0264

AC:

ALSPAC

AF:

0.0278

AC:

107

ESP6500AA

AF:

0.152

AC:

668

ESP6500EA

AF:

0.0281

AC:

242

ExAC

AF:

0.0460

AC:

5588

Asia WGS

AF:

0.0720

AC:

252

AN:

3478

EpiCase

AF:

0.0303

EpiControl

AF:

0.0286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

Cadd

Benign

5.9

Dann

Benign

0.86

DEOGEN2

Benign

0.029

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.00022

P;P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.2

REVEL

Benign

0.14

Sift

Uncertain

0.016

Sift4G

Uncertain

0.032

Polyphen

0.088

Vest4

0.047

MPC

0.12

ClinPred

0.0027

GERP RS

3.3

Varity_R

0.11

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over