rs35949382

Variant names:

• chr22-38989505-T-C
• rs35949382
• NM_004900.5:c.618T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004900.5(APOBEC3B):​c.618T>C​(p.Pro206Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00577 in 1,588,660 control chromosomes in the GnomAD database, including 776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (196 hom., cov: 30)
  • Exomes 𝑓: 0.0045 (580 hom.)
• Consequence: APOBEC3B NM_004900.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.97
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 22-38989505-T-C is Benign according to our data. Variant chr22-38989505-T-C is described in ClinVar as Benign. ClinVar VariationId is 777709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.97 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

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.618T>C	p.Pro206Pro	synonymous	Exon 5 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.618T>C	p.Pro206Pro	synonymous	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.618T>C	p.Pro206Pro	synonymous	Exon 5 of 8	ENSP00000327459.3	Q9UH17-1
	APOBEC3B	ENST00000407298.7	TSL:1	c.618T>C	p.Pro206Pro	synonymous	Exon 5 of 8	ENSP00000385068.3	Q9UH17-3
	APOBEC3B	ENST00000335760.9	TSL:1	n.570-1827T>C		intron	N/A	ENSP00000338897.5	Q9UH17-2

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2715 AN: 148384 Hom.: 195 Cov.: 30

Gnomad AFR AF: 0.0555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00837

Gnomad ASJ AF: 0.00174

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.00135

Gnomad MID AF: 0.0131

Gnomad NFE AF: 0.00326

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00756 AC: 1852 AN: 244828 AF XY: 0.00723

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.00482

Gnomad ASJ exome AF: 0.00339

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00280

Gnomad NFE exome AF: 0.00335

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.00448 AC: 6455 AN: 1440206 Hom.: 580 Cov.: 30 AF XY: 0.00480 AC XY: 3434 AN XY: 715954

African (AFR) AF: 0.0581 AC: 1937 AN: 33332

American (AMR) AF: 0.00505 AC: 211 AN: 41768

Ashkenazi Jewish (ASJ) AF: 0.00315 AC: 82 AN: 26000

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35692

South Asian (SAS) AF: 0.0111 AC: 936 AN: 83974

European-Finnish (FIN) AF: 0.00186 AC: 98 AN: 52786

Middle Eastern (MID) AF: 0.0103 AC: 58 AN: 5606

European-Non Finnish (NFE) AF: 0.00244 AC: 2694 AN: 1101922

Other (OTH) AF: 0.00741 AC: 438 AN: 59126

GnomAD4 genome AF: 0.0183 AC: 2719 AN: 148454 Hom.: 196 Cov.: 30 AF XY: 0.0183 AC XY: 1325 AN XY: 72248

African (AFR) AF: 0.0554 AC: 2265 AN: 40850

American (AMR) AF: 0.00837 AC: 121 AN: 14464

Ashkenazi Jewish (ASJ) AF: 0.00174 AC: 6 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 4422

South Asian (SAS) AF: 0.0128 AC: 57 AN: 4462

European-Finnish (FIN) AF: 0.00135 AC: 14 AN: 10378

Middle Eastern (MID) AF: 0.0140 AC: 4 AN: 286

European-Non Finnish (NFE) AF: 0.00326 AC: 219 AN: 67236

Other (OTH) AF: 0.0163 AC: 33 AN: 2022

Alfa AF: 0.0111 Hom.: 20

Bravo AF: 0.0205

Asia WGS AF: 0.00612 AC: 19 AN: 3116

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs35949382; hg19: chr22-39385510; COSMIC: COSV100213908; COSMIC: COSV100213908;