22-38989518-C-T

Variant names:

• chr22-38989518-C-T
• rs200770515
• NM_004900.5:c.631C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_004900.5(APOBEC3B):​c.631C>T​(p.Arg211Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,588,646 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00036 (5 hom., cov: 30)
  • Exomes 𝑓: 0.00038 (47 hom.)
• Consequence: APOBEC3B NM_004900.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.21
• Publications: 5 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015589505).
• BP6: Variant 22-38989518-C-T is Benign according to our data. Variant chr22-38989518-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1048995.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 5 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.631C>T	p.Arg211Trp	missense	Exon 5 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.631C>T	p.Arg211Trp	missense	Exon 5 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.631C>T	p.Arg211Trp	missense	Exon 5 of 8	ENSP00000327459.3	Q9UH17-1
	APOBEC3B	ENST00000407298.7	TSL:1	c.631C>T	p.Arg211Trp	missense	Exon 5 of 8	ENSP00000385068.3	Q9UH17-3
	APOBEC3B	ENST00000335760.9	TSL:1	n.570-1814C>T		intron	N/A	ENSP00000338897.5	Q9UH17-2

Frequencies

GnomAD3 genomes AF: 0.000364 AC: 54 AN: 148486 Hom.: 5 Cov.: 30

Gnomad AFR AF: 0.0000980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000899

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: 0.000535

Gnomad OTH AF: 0.000496

GnomAD2 exomes AF: 0.000315 AC: 77 AN: 244816 AF XY: 0.000279

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000809

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000416

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000380 AC: 547 AN: 1440088 Hom.: 47 Cov.: 30 AF XY: 0.000390 AC XY: 279 AN XY: 715916

African (AFR) AF: 0.0000600 AC: 2 AN: 33340

American (AMR) AF: 0.000790 AC: 33 AN: 41772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 35690

South Asian (SAS) AF: 0.0000357 AC: 3 AN: 83946

European-Finnish (FIN) AF: 0.0000758 AC: 4 AN: 52774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.000445 AC: 490 AN: 1101882

Other (OTH) AF: 0.000254 AC: 15 AN: 59112

GnomAD4 genome AF: 0.000363 AC: 54 AN: 148558 Hom.: 5 Cov.: 30 AF XY: 0.000360 AC XY: 26 AN XY: 72290

African (AFR) AF: 0.0000978 AC: 4 AN: 40920

American (AMR) AF: 0.000898 AC: 13 AN: 14470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 4420

South Asian (SAS) AF: 0.00 AC: 0 AN: 4474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000535 AC: 36 AN: 67276

Other (OTH) AF: 0.000497 AC: 1 AN: 2014

Alfa AF: 0.000383 Hom.: 3

Bravo AF: 0.000310

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000351 AC: 3

ExAC AF: 0.000235 AC: 28

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-1.2
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Benign	0.040	D
Sift4G	Uncertain	0.021	D
Polyphen		0.021	B
Vest4		0.28
MVP		0.65
MPC		0.25
ClinPred		0.055	T
GERP RS		-0.30
Varity_R		0.24
gMVP		0.68
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs200770515; hg19: chr22-39385523; COSMIC: COSV59841187; COSMIC: COSV59841187;