Genetic Variant NM_004900.5:c.799T>C (chr22-38991407-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_004900.5(APOBEC3B):c.799T>C(p.Leu267Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,572,318 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0014 ( 13 hom. )

Consequence

APOBEC3B
NM_004900.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00900

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP7

Synonymous conserved (PhyloP=-0.009 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3B	NM_004900.5 link	c.799T>C	p.Leu267Leu	synonymous_variant	Exon 6 of 8	ENST00000333467.4	NP_004891.5	Q9UH17-1
APOBEC3B	NM_001270411.2 link	c.724T>C	p.Leu242Leu	splice_region_variant, synonymous_variant	Exon 6 of 8		NP_001257340.2	Q9UH17-3
APOBEC3B-AS1	NR_104187.1 link	n.*152A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3B	ENST00000333467.4 link	c.799T>C	p.Leu267Leu	synonymous_variant	Exon 6 of 8	1	NM_004900.5	ENSP00000327459.3		Q9UH17-1

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

250

AN:

146236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00426

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000789

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000231

Gnomad SAS

AF:

0.000227

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.000875

Gnomad OTH

AF:

0.00152

GnomAD3 exomes

AF:

0.000969

AC:

233

AN:

240558

Hom.:

AF XY:

0.000893

AC XY:

117

AN XY:

131072

show subpopulations

Gnomad AFR exome

AF:

0.00516

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000125

Gnomad SAS exome

AF:

0.000201

Gnomad FIN exome

AF:

0.0000472

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.00143

AC:

2038

AN:

1426006

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

988

AN XY:

710232

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.000788

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.000155

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00175

AC:

256

AN:

146312

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

128

AN XY:

71084

show subpopulations

Gnomad4 AFR

AF:

0.00437

Gnomad4 AMR

AF:

0.000789

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000232

Gnomad4 SAS

AF:

0.000227

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000875

Gnomad4 OTH

AF:

0.00152

Alfa

AF:

0.000392

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.75

DANN

Benign

0.36

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over