22-38985899-A-G

Variant names:

• chr22-38985899-A-G
• rs151303359
• NM_004900.5:c.262A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004900.5(APOBEC3B):​c.262A>G​(p.Ile88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 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. I88L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOBEC3B NM_004900.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004900.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3B	NM_004900.5	MANE Select	c.262A>G	p.Ile88Val	missense	Exon 3 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.262A>G	p.Ile88Val	missense	Exon 3 of 8	NP_001257340.2	Q9UH17-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3B	ENST00000333467.4	TSL:1 MANE Select	c.262A>G	p.Ile88Val	missense	Exon 3 of 8	ENSP00000327459.3	Q9UH17-1
	APOBEC3B	ENST00000407298.7	TSL:1	c.262A>G	p.Ile88Val	missense	Exon 3 of 8	ENSP00000385068.3	Q9UH17-3
	APOBEC3B	ENST00000335760.9	TSL:1	n.262A>G		non_coding_transcript_exon	Exon 3 of 7	ENSP00000338897.5	Q9UH17-2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248810 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.89e-7 AC: 1 AN: 1452040 Hom.: 0 Cov.: 81 AF XY: 0.00 AC XY: 0 AN XY: 722312

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.0000229 AC: 1 AN: 43656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 36792

South Asian (SAS) AF: 0.00 AC: 0 AN: 85068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108458

Other (OTH) AF: 0.00 AC: 0 AN: 59808

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	1.8
DANN	Benign	0.15
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00079	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.43
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.018	B
Vest4		0.19
MutPred		0.64		Gain of sheet (P = 0.1208)
MVP		0.49
MPC		2.1
ClinPred		0.054	T
GERP RS		-4.3
Varity_R		0.072
gMVP		0.14
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs151303359; hg19: chr22-39381904;