rs17000697

Positions:

• chr22-38985962-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004900.5(APOBEC3B):​c.325T>G​(p.Ser109Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,599,074 control chromosomes in the GnomAD database, including 447 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0046 (35 hom., cov: 28)
  • Exomes 𝑓: 0.0053 (412 hom.)
• Consequence: APOBEC3B NM_004900.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006128192).
• BP6: Variant 22-38985962-T-G is Benign according to our data. Variant chr22-38985962-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3B	NM_004900.5	c.325T>G	p.Ser109Ala	missense_variant	3/8	ENST00000333467.4	NP_004891.5
APOBEC3B	NM_001270411.2	c.325T>G	p.Ser109Ala	missense_variant	3/8		NP_001257340.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3B	ENST00000333467.4	c.325T>G	p.Ser109Ala	missense_variant	3/8	1	NM_004900.5	ENSP00000327459	P2
APOBEC3B	ENST00000407298.7	c.325T>G	p.Ser109Ala	missense_variant	3/8	1		ENSP00000385068
APOBEC3B	ENST00000335760.9	c.325T>G	p.Ser109Ala	missense_variant, NMD_transcript_variant	3/7	1		ENSP00000338897
APOBEC3B	ENST00000402182.7	c.325T>G	p.Ser109Ala	missense_variant	3/7	2		ENSP00000385060	A2

Frequencies

GnomAD3 genomes AF: 0.00463 AC: 684 AN: 147604 Hom.: 35 Cov.: 28

Gnomad AFR AF: 0.00429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.000579

Gnomad EAS AF: 0.000692

Gnomad SAS AF: 0.00317

Gnomad FIN AF: 0.000777

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00659

Gnomad OTH AF: 0.00555

GnomAD3 exomes AF: 0.00302 AC: 752 AN: 248958 Hom.: 43 AF XY: 0.00329 AC XY: 443 AN XY: 134590

Gnomad AFR exome AF: 0.00235

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.000287

Gnomad SAS exome AF: 0.00267

Gnomad FIN exome AF: 0.00186

Gnomad NFE exome AF: 0.00438

Gnomad OTH exome AF: 0.00362

GnomAD4 exome AF: 0.00526 AC: 7638 AN: 1451398 Hom.: 412 Cov.: 84 AF XY: 0.00525 AC XY: 3792 AN XY: 721974

Gnomad4 AFR exome AF: 0.00357

Gnomad4 AMR exome AF: 0.00193

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.000380

Gnomad4 SAS exome AF: 0.00305

Gnomad4 FIN exome AF: 0.00190

Gnomad4 NFE exome AF: 0.00608

Gnomad4 OTH exome AF: 0.00490

GnomAD4 genome AF: 0.00465 AC: 686 AN: 147676 Hom.: 35 Cov.: 28 AF XY: 0.00434 AC XY: 312 AN XY: 71832

Gnomad4 AFR AF: 0.00433

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.000579

Gnomad4 EAS AF: 0.000695

Gnomad4 SAS AF: 0.00317

Gnomad4 FIN AF: 0.000777

Gnomad4 NFE AF: 0.00659

Gnomad4 OTH AF: 0.00556

Alfa AF: 0.00513 Hom.: 11

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00314 AC: 27

ExAC AF: 0.00366 AC: 444

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

APOBEC3A: BS2; APOBEC3B: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.023
DANN	Benign	0.16
DEOGEN2	Benign	0.0011	.;T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.18	T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.0061	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.4	N;N;N
REVEL	Benign	0.088
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.069
MVP		0.29
MPC		1.1
ClinPred		0.00028	T
GERP RS		-2.9
Varity_R		0.087
gMVP		0.091

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

Other links and lift over

dbSNP: rs17000697; hg19: chr22-39381967;