dbSNP rs34275479: APOBEC1:p.Trp21* (chr12-7652818-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

13 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 -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 VariationId is 2642680.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

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.62G>A	p.Trp21*	stop_gained	Exon 3 of 5	NP_001635.2	P41238
APOBEC1	NM_001304566.1		c.62G>A	p.Trp21*	stop_gained	Exon 4 of 6	NP_001291495.1	P41238
APOBEC1	NM_005889.4		c.-74G>A		5_prime_UTR	Exon 2 of 4	NP_005880.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC1	ENST00000229304.5	TSL:1 MANE Select	c.62G>A	p.Trp21*	stop_gained	Exon 3 of 5	ENSP00000229304.4	P41238
	APOBEC1	ENST00000467171.2	TSL:1	n.34G>A		non_coding_transcript_exon	Exon 2 of 4	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

GnomAD2 exomes

AF:

0.00589

AC:

1391

AN:

236318

AF XY:

0.00622

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 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

African (AFR)

AF:

0.00148

AC:

AN:

32354

American (AMR)

AF:

0.00130

AC:

AN:

41386

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

25430

East Asian (EAS)

AF:

0.0000508

AC:

AN:

39346

South Asian (SAS)

AF:

0.00610

AC:

509

AN:

83430

European-Finnish (FIN)

AF:

0.00249

AC:

128

AN:

51356

Middle Eastern (MID)

AF:

0.00230

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00999

AC:

10998

AN:

1100706

Other (OTH)

AF:

0.00654

AC:

388

AN:

59348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

647

1294

1941

2588

3235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.00554

AC:

844

AN:

152332

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41582

American (AMR)

AF:

0.00170

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00497

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00983

AC:

669

AN:

68036

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

135

180

225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00840

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Uncertain

0.41

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.036

PhyloP100

-0.019

Vest4

0.85

GERP RS

3.6

Mutation Taster

=163/37

disease causing (fs/PTC)

(source)

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

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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