chr22-38985899-A-C

Position:

chr22-38985899-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000333467.4(APOBEC3B):c.262A>C(p.Ile88Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,599,610 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 55 hom., cov: 28)

Exomes 𝑓: 0.00072 ( 41 hom. )

Consequence

APOBEC3B
ENST00000333467.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.431

Variant links:

Genes affected

APOBEC3B (HGNC:17352): (apolipoprotein B mRNA editing enzyme catalytic subunit 3B) This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. It is thought that the proteins may be RNA editing enzymes and have roles in growth or cell cycle control. A hybrid gene results from the deletion of approximately 29.5 kb of sequence between this gene, APOBEC3B, and the adjacent gene APOBEC3A. The breakpoints of the deletion are within the two genes, so the deletion allele is predicted to have the promoter and coding region of APOBEC3A, but the 3' UTR of APOBEC3B. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

APOBEC3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009643048).

BP6

Variant 22-38985899-A-C is Benign according to our data. Variant chr22-38985899-A-C is described in ClinVar as [Benign]. Clinvar id is 1050592.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00745 (1100/147588) while in subpopulation AFR AF= 0.0256 (1040/40552). AF 95% confidence interval is 0.0244. There are 55 homozygotes in gnomad4. There are 501 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 linkuse as main transcript	c.262A>C	p.Ile88Leu	missense_variant	3/8	ENST00000333467.4	NP_004891.5
APOBEC3B	NM_001270411.2 linkuse as main transcript	c.262A>C	p.Ile88Leu	missense_variant	3/8		NP_001257340.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3B	ENST00000333467.4 linkuse as main transcript	c.262A>C	p.Ile88Leu	missense_variant	3/8	1	NM_004900.5	ENSP00000327459	P2	Q9UH17-1
APOBEC3B	ENST00000407298.7 linkuse as main transcript	c.262A>C	p.Ile88Leu	missense_variant	3/8	1		ENSP00000385068		Q9UH17-3
APOBEC3B	ENST00000335760.9 linkuse as main transcript	c.262A>C	p.Ile88Leu	missense_variant, NMD_transcript_variant	3/7	1		ENSP00000338897		Q9UH17-2
APOBEC3B	ENST00000402182.7 linkuse as main transcript	c.262A>C	p.Ile88Leu	missense_variant	3/7	2		ENSP00000385060	A2

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

1099

AN:

147516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00280

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000149

Gnomad OTH

AF:

0.00453

GnomAD3 exomes

AF:

0.00211

AC:

526

AN:

248810

Hom.:

AF XY:

0.00155

AC XY:

208

AN XY:

134608

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000720

AC:

1045

AN:

1452022

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

456

AN XY:

722300

show subpopulations

Gnomad4 AFR exome

AF:

0.0228

Gnomad4 AMR exome

AF:

0.00160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000848

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00745

AC:

1100

AN:

147588

Hom.:

Cov.:

AF XY:

0.00698

AC XY:

501

AN XY:

71760

show subpopulations

Gnomad4 AFR

AF:

0.0256

Gnomad4 AMR

AF:

0.00280

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000149

Gnomad4 OTH

AF:

0.00454

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00805

ESP6500AA

AF:

0.0261

AC:

115

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00245

AC:

297

EpiCase

AF:

0.0000548

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

The APOBEC3B p.Ile88Leu variant was not identified in the literature nor was it identified in ClinVar or Cosmic. The variant was identified in dbSNP (ID: rs151303359) and LOVD 3.0. The variant was identified in control databases in 759 of 279140 chromosomes (28 homozygous) at a frequency of 0.002719 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 680 of 24728 chromosomes (freq: 0.0275), Latino in 50 of 34640 chromosomes (freq: 0.001443), Other in 10 of 7134 chromosomes (freq: 0.001402) and European (non-Finnish) in 19 of 128516 chromosomes (freq: 0.000148), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.Ile88 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.7

DANN

Benign

0.86

DEOGEN2

Benign

0.027

.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

2.0

M;.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.081

T;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.14

.;.;B

Vest4

0.46

MVP

0.53

MPC

2.3

ClinPred

0.018

GERP RS

-4.3

Varity_R

0.50

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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