rs151303359

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-38985899-A-C
• chr22-38985899-A-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004900.5(APOBEC3B):​c.262A>C​(p.Ile88Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,599,610 control chromosomes in the GnomAD database, including 96 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (55 hom., cov: 28)
  • Exomes 𝑓: 0.00072 (41 hom.)
• Consequence: APOBEC3B NM_004900.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009643048).
• BP6: Variant 22-38985899-A-C is Benign according to our data. Variant chr22-38985899-A-C is described in ClinVar as Benign. ClinVar VariationId is 1050592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00745 (1100/147588) while in subpopulation AFR AF = 0.0256 (1040/40552). AF 95% confidence interval is 0.0244. There are 55 homozygotes in GnomAd4. There are 501 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 55 AR gene

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>C	p.Ile88Leu	missense	Exon 3 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.262A>C	p.Ile88Leu	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>C	p.Ile88Leu	missense	Exon 3 of 8	ENSP00000327459.3	Q9UH17-1
	APOBEC3B	ENST00000407298.7	TSL:1	c.262A>C	p.Ile88Leu	missense	Exon 3 of 8	ENSP00000385068.3	Q9UH17-3
	APOBEC3B	ENST00000335760.9	TSL:1	n.262A>C		non_coding_transcript_exon	Exon 3 of 7	ENSP00000338897.5	Q9UH17-2

Frequencies

GnomAD3 genomes AF: 0.00745 AC: 1099 AN: 147516 Hom.: 56 Cov.: 28

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00280

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000149

Gnomad OTH AF: 0.00453

GnomAD2 exomes AF: 0.00211 AC: 526 AN: 248810 AF XY: 0.00155

Gnomad AFR exome AF: 0.0278

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000720 AC: 1045 AN: 1452022 Hom.: 41 Cov.: 81 AF XY: 0.000631 AC XY: 456 AN XY: 722300

African (AFR) AF: 0.0228 AC: 761 AN: 33366

American (AMR) AF: 0.00160 AC: 70 AN: 43654

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

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

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85068

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

Middle Eastern (MID) AF: 0.00140 AC: 8 AN: 5718

European-Non Finnish (NFE) AF: 0.0000848 AC: 94 AN: 1108458

Other (OTH) AF: 0.00186 AC: 111 AN: 59808

GnomAD4 genome AF: 0.00745 AC: 1100 AN: 147588 Hom.: 55 Cov.: 28 AF XY: 0.00698 AC XY: 501 AN XY: 71760

African (AFR) AF: 0.0256 AC: 1040 AN: 40552

American (AMR) AF: 0.00280 AC: 40 AN: 14296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 4346

South Asian (SAS) AF: 0.00 AC: 0 AN: 4428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10240

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000149 AC: 10 AN: 67120

Other (OTH) AF: 0.00454 AC: 9 AN: 1984

Alfa AF: 0.00157 Hom.: 3

Bravo AF: 0.00805

ESP6500AA AF: 0.0261 AC: 115

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00245 AC: 297

EpiCase AF: 0.0000548

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.7
DANN	Benign	0.86
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.43
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.081	T
Sift4G	Uncertain	0.011	D
Polyphen		0.14	B
Vest4		0.46
MVP		0.53
MPC		2.3
ClinPred		0.018	T
GERP RS		-4.3
Varity_R		0.50
gMVP		0.37
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs151303359; hg19: chr22-39381904; COSMIC: COSV107364166;