Variant 1-183648268-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_203454.3(APOBEC4):c.514G>A(p.Glu172Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

APOBEC4
NM_203454.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062746316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC4	NM_203454.3 linkuse as main transcript	c.514G>A	p.Glu172Lys	missense_variant	2/2	ENST00000308641.6	NP_982279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC4	ENST00000308641.6 linkuse as main transcript	c.514G>A	p.Glu172Lys	missense_variant	2/2	1	NM_203454.3	ENSP00000310622	P1
RGL1	ENST00000304685.8 linkuse as main transcript	c.-33+11767C>T		intron_variant		1		ENSP00000303192		Q9NZL6-2
APOBEC4	ENST00000481562.1 linkuse as main transcript	n.246-471G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000756

AC:

AN:

251284

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

278

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000241

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000230

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2021

The c.514G>A (p.E172K) alteration is located in exon 2 (coding exon 1) of the APOBEC4 gene. This alteration results from a G to A substitution at nucleotide position 514, causing the glutamic acid (E) at amino acid position 172 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.69

M_CAP

Benign

0.014

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.99

D;D;D;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.68

REVEL

Benign

0.037

Sift

Benign

0.29

Sift4G

Benign

0.35

Polyphen

0.56

Vest4

0.16

MVP

0.35

MPC

0.15

ClinPred

0.020

GERP RS

3.1

Varity_R

0.049

gMVP

0.71

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over