dbSNP rs780014617: APOBEC3B:p.Ala242Thr (chr22-38991332-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004900.5(APOBEC3B):c.724G>A(p.Ala242Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000679 in 147,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A242S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APOBEC3B
NM_004900.5 missense, splice_region

Scores

Splicing: ADA: 0.0004468

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

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:

APOBEC3B-AS1 (HGNC:43836): (APOBEC3B antisense RNA 1)

APOBEC3B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07112762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 link	c.724G>A	p.Ala242Thr	missense_variant, splice_region_variant	Exon 6 of 8	ENST00000333467.4	NP_004891.5	Q9UH17-1
APOBEC3B	NM_001270411.2 link	c.724-75G>A		intron_variant	Intron 5 of 7		NP_001257340.2	Q9UH17-3
APOBEC3B-AS1	NR_104187.1 link	n.*227C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3B	ENST00000333467.4 link	c.724G>A	p.Ala242Thr	missense_variant, splice_region_variant	Exon 6 of 8	1	NM_004900.5	ENSP00000327459.3		Q9UH17-1

Frequencies

GnomAD3 genomes

AF:

0.00000679

AC:

AN:

147198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000887

AC:

AN:

225540

Hom.:

AF XY:

0.00000809

AC XY:

AN XY:

123594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000230

AC:

AN:

1345624

Hom.:

Cov.:

AF XY:

0.0000164

AC XY:

AN XY:

672470

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000285

Gnomad4 OTH exome

AF:

0.0000179

GnomAD4 genome

AF:

0.00000679

AC:

AN:

147198

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71562

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.6

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.066

Sift

Benign

0.12

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.025

.;B

Vest4

0.23

MVP

0.30

MPC

2.8

ClinPred

0.057

GERP RS

-1.3

Varity_R

0.067

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00045

dbscSNV1_RF

Benign

0.094

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over