Genetic Variant NM_001644.5:c.472A>G (chr12-7651112-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001644.5(APOBEC1):c.472A>G(p.Asn158Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

APOBEC1
NM_001644.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.333

Publications

0 publications found

Variant links:

Genes affected

APOBEC1 (HGNC:604): (apolipoprotein B mRNA editing enzyme catalytic subunit 1) This gene encodes a member of the cytidine deaminase enzyme family. The encoded protein forms a multiple-protein editing holoenzyme with APOBEC1 complementation factor (ACF) and APOBEC1 stimulating protein (ASP). This holoenzyme is involved in the editing of C-to-U nucleotide bases in apolipoprotein B and neurofibromatosis-1 mRNAs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

APOBEC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06537917).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001644.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOBEC1	NM_001644.5	MANE Select	c.472A>G	p.Asn158Asp	missense	Exon 4 of 5	NP_001635.2	P41238
APOBEC1	NM_001304566.1		c.472A>G	p.Asn158Asp	missense	Exon 5 of 6	NP_001291495.1	P41238
APOBEC1	NM_005889.4		c.337A>G	p.Asn113Asp	missense	Exon 3 of 4	NP_005880.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APOBEC1	ENST00000229304.5	TSL:1 MANE Select	c.472A>G	p.Asn158Asp	missense	Exon 4 of 5	ENSP00000229304.4	P41238
APOBEC1	ENST00000467171.2	TSL:1	n.*333A>G		non_coding_transcript_exon	Exon 3 of 4	ENSP00000436415.2	A0A0B4J232
APOBEC1	ENST00000467171.2	TSL:1	n.*333A>G		3_prime_UTR	Exon 3 of 4	ENSP00000436415.2	A0A0B4J232

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251476

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.000157

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111918

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41510

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.031

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.63

M_CAP

Benign

0.0049

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

PhyloP100

0.33

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.30

REVEL

Benign

0.18

Sift

Benign

0.79

Sift4G

Benign

0.32

Polyphen

0.0050

Vest4

0.15

MVP

0.57

MPC

0.40

ClinPred

0.051

GERP RS

3.6

Varity_R

0.19

gMVP

0.59

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over