Genetic Variant APOBEC1:p.Trp21* (chr12-7652818-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001644.5(APOBEC1):c.62G>A(p.Trp21*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0082 in 1,591,334 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 65 hom. )

Consequence

APOBEC1
NM_001644.5 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0190

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 12-7652818-C-T is Benign according to our data. Variant chr12-7652818-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642680.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC1	NM_001644.5 link	c.62G>A	p.Trp21*	stop_gained	Exon 3 of 5	ENST00000229304.5	NP_001635.2	P41238
APOBEC1	NM_001304566.1 link	c.62G>A	p.Trp21*	stop_gained	Exon 4 of 6		NP_001291495.1	P41238
APOBEC1	NM_005889.4 link	c.-74G>A		5_prime_UTR_variant	Exon 2 of 4		NP_005880.2	P41238

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC1	ENST00000229304.5 link	c.62G>A	p.Trp21*	stop_gained	Exon 3 of 5	1	NM_001644.5	ENSP00000229304.4		P41238
APOBEC1	ENST00000467171.2 link	n.34G>A		non_coding_transcript_exon_variant	Exon 2 of 4	1		ENSP00000436415.2		A0A0B4J232

Frequencies

GnomAD3 genomes

AF:

0.00554

AC:

844

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00983

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00589

AC:

1391

AN:

236318

Hom.:

AF XY:

0.00622

AC XY:

799

AN XY:

128466

show subpopulations

Gnomad AFR exome

AF:

0.00243

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.000228

Gnomad SAS exome

AF:

0.00622

Gnomad FIN exome

AF:

0.00262

Gnomad NFE exome

AF:

0.00949

Gnomad OTH exome

AF:

0.00404

GnomAD4 exome

AF:

0.00848

AC:

12205

AN:

1439002

Hom.:

Cov.:

AF XY:

0.00853

AC XY:

6085

AN XY:

713220

show subpopulations

Gnomad4 AFR exome

AF:

0.00148

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00610

Gnomad4 FIN exome

AF:

0.00249

Gnomad4 NFE exome

AF:

0.00999

Gnomad4 OTH exome

AF:

0.00654

GnomAD4 genome

AF:

0.00554

AC:

844

AN:

152332

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00983

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00851

Hom.:

Bravo

AF:

0.00524

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00803

AC:

ExAC

AF:

0.00591

AC:

717

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

APOBEC1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Uncertain

0.41

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.036

Vest4

0.85

GERP RS

3.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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