22-38989518-C-T

Position:

chr22-38989518-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004900.5(APOBEC3B):c.631C>T(p.Arg211Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,588,646 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00036 ( 5 hom., cov: 30)

Exomes 𝑓: 0.00038 ( 47 hom. )

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.21

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015589505).

BP6

Variant 22-38989518-C-T is Benign according to our data. Variant chr22-38989518-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1048995.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/8	ENST00000333467.4	NP_004891.5	Q9UH17-1
APOBEC3B	NM_001270411.2 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/8		NP_001257340.2	Q9UH17-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APOBEC3B	ENST00000333467.4 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/8	1	NM_004900.5	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/8	1		ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9 linkuse as main transcript	n.570-1814C>T		intron_variant		1		ENSP00000338897.5	Q9UH17-2
APOBEC3B	ENST00000402182.7 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/7	2		ENSP00000385060.3	B0QYD3

Frequencies

GnomAD3 genomes

AF:

0.000364

AC:

AN:

148486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000899

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:

0.000535

Gnomad OTH

AF:

0.000496

GnomAD3 exomes

AF:

0.000315

AC:

AN:

244816

Hom.:

AF XY:

0.000279

AC XY:

AN XY:

132708

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000809

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000416

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000380

AC:

547

AN:

1440088

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

279

AN XY:

715916

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000790

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000357

Gnomad4 FIN exome

AF:

0.0000758

Gnomad4 NFE exome

AF:

0.000445

Gnomad4 OTH exome

AF:

0.000254

GnomAD4 genome

AF:

0.000363

AC:

AN:

148558

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

AN XY:

72290

show subpopulations

Gnomad4 AFR

AF:

0.0000978

Gnomad4 AMR

AF:

0.000898

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000535

Gnomad4 OTH

AF:

0.000497

Alfa

AF:

0.000383

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000351

AC:

ExAC

AF:

0.000235

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

The APOBEC3B p.Arg211Trp variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs200770515) and in COSMIC database (FATHMM prediction of neutral; score=0.01). The variant was identified in control databases in 87 of 275244 chromosomes (8 homozygous) at a frequency of 0.000316 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 29 of 32938 chromosomes (freq: 0.00088), European (non-Finnish) in 53 of 128060 chromosomes (freq: 0.000414), South Asian in 3 of 29926 chromosomes (freq: 0.0001) and African in 2 of 24720 chromosomes (freq: 0.000081); it was not observed in the Ashkenazi Jewish, East Asian, European (Finnish) or Other populations. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Arg211 residue is not conserved in mammals or distantly related organisms 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. 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

0.17

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.088

.;T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.3

M;.;M

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.040

D;D;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.021

.;.;B

Vest4

0.28

MVP

0.65

MPC

0.25

ClinPred

0.055

GERP RS

-0.30

Varity_R

0.24

gMVP

0.68

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

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