22-38984126-C-T

Position:

• chr22-38984126-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000333467.4(APOBEC3B):​c.69C>T​(p.Asn23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,589,576 control chromosomes in the GnomAD database, including 516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (261 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (255 hom.)
• Consequence: APOBEC3B ENST00000333467.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.271

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 22-38984126-C-T is Benign according to our data. Variant chr22-38984126-C-T is described in ClinVar as [Benign]. Clinvar id is 778951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.271 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3B	NM_004900.5	c.69C>T	p.Asn23=	synonymous_variant	2/8	ENST00000333467.4	NP_004891.5
APOBEC3B	NM_001270411.2	c.69C>T	p.Asn23=	synonymous_variant	2/8		NP_001257340.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3B	ENST00000333467.4	c.69C>T	p.Asn23=	synonymous_variant	2/8	1	NM_004900.5	ENSP00000327459	P2
APOBEC3B	ENST00000407298.7	c.69C>T	p.Asn23=	synonymous_variant	2/8	1		ENSP00000385068
APOBEC3B	ENST00000335760.9	c.69C>T	p.Asn23=	synonymous_variant, NMD_transcript_variant	2/7	1		ENSP00000338897
APOBEC3B	ENST00000402182.7	c.69C>T	p.Asn23=	synonymous_variant	2/7	2		ENSP00000385060	A2

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2917 AN: 148614 Hom.: 260 Cov.: 31

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00686

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000442

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000371

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00538 AC: 1296 AN: 240788 Hom.: 101 AF XY: 0.00406 AC XY: 531 AN XY: 130856

Gnomad AFR exome AF: 0.0677

Gnomad AMR exome AF: 0.00348

Gnomad ASJ exome AF: 0.000405

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000306

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.000608

Gnomad OTH exome AF: 0.00404

GnomAD4 exome AF: 0.00219 AC: 3150 AN: 1440892 Hom.: 255 Cov.: 31 AF XY: 0.00187 AC XY: 1338 AN XY: 716956

Gnomad4 AFR exome AF: 0.0675

Gnomad4 AMR exome AF: 0.00464

Gnomad4 ASJ exome AF: 0.000231

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000227

Gnomad4 FIN exome AF: 0.000170

Gnomad4 NFE exome AF: 0.000337

Gnomad4 OTH exome AF: 0.00473

GnomAD4 genome AF: 0.0197 AC: 2925 AN: 148684 Hom.: 261 Cov.: 31 AF XY: 0.0197 AC XY: 1427 AN XY: 72366

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.00685

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000443

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000371

Gnomad4 OTH AF: 0.0148

Alfa AF: 0.0101 Hom.: 20

Bravo AF: 0.0216

EpiCase AF: 0.000274

EpiControl AF: 0.000717

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.50

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: rs113972364; hg19: chr22-39380131;