22-38984190-C-T

Position:

chr22-38984190-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004900.5(APOBEC3B):c.133C>T(p.Arg45Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,592,538 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 16 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 199 hom. )

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -5.58

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006023586).

BP6

Variant 22-38984190-C-T is Benign according to our data. Variant chr22-38984190-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1049516.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 link	c.133C>T	p.Arg45Cys	missense_variant	2/8	ENST00000333467.4	NP_004891.5	Q9UH17-1
APOBEC3B	NM_001270411.2 link	c.133C>T	p.Arg45Cys	missense_variant	2/8		NP_001257340.2	Q9UH17-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOBEC3B	ENST00000333467.4 link	c.133C>T	p.Arg45Cys	missense_variant	2/8	1	NM_004900.5	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7 link	c.133C>T	p.Arg45Cys	missense_variant	2/8	1		ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9 link	n.133C>T		non_coding_transcript_exon_variant	2/7	1		ENSP00000338897.5	Q9UH17-2
APOBEC3B	ENST00000402182.7 link	c.133C>T	p.Arg45Cys	missense_variant	2/7	2		ENSP00000385060.3	B0QYD3

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

357

AN:

148570

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000970

Gnomad ASJ

AF:

0.00405

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00111

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00149

GnomAD3 exomes

AF:

0.00178

AC:

434

AN:

243456

Hom.:

AF XY:

0.00181

AC XY:

239

AN XY:

132106

show subpopulations

Gnomad AFR exome

AF:

0.00466

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00491

Gnomad EAS exome

AF:

0.000251

Gnomad SAS exome

AF:

0.00138

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00196

AC:

2823

AN:

1443898

Hom.:

199

Cov.:

AF XY:

0.00194

AC XY:

1393

AN XY:

718346

show subpopulations

Gnomad4 AFR exome

AF:

0.00390

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00488

Gnomad4 EAS exome

AF:

0.000223

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.0000567

Gnomad4 NFE exome

AF:

0.00200

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00240

AC:

357

AN:

148640

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

174

AN XY:

72344

show subpopulations

Gnomad4 AFR

AF:

0.00500

Gnomad4 AMR

AF:

0.000970

Gnomad4 ASJ

AF:

0.00405

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00111

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00149

Alfa

AF:

0.00237

Hom.:

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00432

AC:

ESP6500EA

AF:

0.00210

AC:

ExAC

AF:

0.00172

AC:

205

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	The APOBEC3B p.Arg45Cys variant was not identified in the literature nor was it identified in ClinVar or Cosmic. The variant was identified in dbSNP (ID: rs143126732) and in control databases in 524 of 274044 chromosomes (34 homozygous) at a frequency of 0.001912 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 141 of 24676 chromosomes (freq: 0.005714), Ashkenazi Jewish in 50 of 10272 chromosomes (freq: 0.004868), European (non-Finnish) in 232 of 127740 chromosomes (freq: 0.001816), Latino in 47 of 32462 chromosomes (freq: 0.001448), South Asian in 41 of 29784 chromosomes (freq: 0.001377), Other in 8 of 7072 chromosomes (freq: 0.001131), East Asian in 4 of 17200 chromosomes (freq: 0.000233) and European (Finnish) in 1 of 24838 chromosomes (freq: 0.00004). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Arg45 residue is not conserved in mammals or other organisms and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.17

DANN

Benign

0.84

DEOGEN2

Benign

0.014

.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.44

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.0060

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.084

Sift

Benign

0.045

D;T;D

Sift4G

Benign

0.081

T;T;T

Polyphen

0.0080

.;.;B

Vest4

0.18

MVP

0.40

MPC

1.9

ClinPred

0.018

GERP RS

-4.9

Varity_R

0.19

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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