NM_004900.5:c.547C>T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004900.5(APOBEC3B):c.547C>T(p.Arg183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,593,644 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 1 hom., cov: 30)

Exomes 𝑓: 0.000046 ( 6 hom. )

Consequence

APOBEC3B
NM_004900.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.45

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.079337835).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 link	c.547C>T	p.Arg183Cys	missense_variant	Exon 4 of 8	ENST00000333467.4	NP_004891.5	Q9UH17-1
APOBEC3B	NM_001270411.2 link	c.547C>T	p.Arg183Cys	missense_variant	Exon 4 of 8		NP_001257340.2	Q9UH17-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOBEC3B	ENST00000333467.4 link	c.547C>T	p.Arg183Cys	missense_variant	Exon 4 of 8	1	NM_004900.5	ENSP00000327459.3	Q9UH17-1
APOBEC3B	ENST00000407298.7 link	c.547C>T	p.Arg183Cys	missense_variant	Exon 4 of 8	1		ENSP00000385068.3	Q9UH17-3
APOBEC3B	ENST00000335760.9 link	n.547C>T		non_coding_transcript_exon_variant	Exon 4 of 7	1		ENSP00000338897.5	Q9UH17-2
APOBEC3B	ENST00000402182.7 link	c.547C>T	p.Arg183Cys	missense_variant	Exon 4 of 7	2		ENSP00000385060.3	B0QYD3

Frequencies

GnomAD3 genomes

AF:

0.0000336

AC:

AN:

148850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000688

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:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000735

AC:

AN:

244964

Hom.:

AF XY:

0.000113

AC XY:

AN XY:

132776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000620

Gnomad SAS exome

AF:

0.0000668

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000457

AC:

AN:

1444794

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

718820

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000477

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000278

Gnomad4 SAS exome

AF:

0.0000831

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000434

Gnomad4 OTH exome

AF:

0.0000841

GnomAD4 genome

AF:

0.0000336

AC:

AN:

148850

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72418

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.0000688

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000446

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000775

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000667

AC:

EpiCase

AF:

0.000110

EpiControl

AF:

0.000179

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.547C>T (p.R183C) alteration is located in exon 4 (coding exon 4) of the APOBEC3B gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.12

DANN

Benign

0.80

DEOGEN2

Benign

0.021

.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.10

T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;L

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.6

D;N;N

REVEL

Benign

0.095

Sift

Benign

0.19

T;D;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.17

MVP

0.48

MPC

0.51

ClinPred

0.023

GERP RS

-4.3

Varity_R

0.11

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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