22-38991407-T-C

Variant names:

• chr22-38991407-T-C
• rs142595375
• NM_004900.5:c.799T>C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001270411.2(APOBEC3B):​c.724T>C​(p.Leu242Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,572,318 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0014 (13 hom.)
• Consequence: APOBEC3B NM_001270411.2 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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]

APOBEC3B-AS1 (HGNC:43836): (APOBEC3B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP7: Synonymous conserved (PhyloP=-0.009 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3B	NM_004900.5	c.799T>C	p.Leu267Leu	synonymous_variant	Exon 6 of 8	ENST00000333467.4	NP_004891.5
APOBEC3B	NM_001270411.2	c.724T>C	p.Leu242Leu	splice_region_variant, synonymous_variant	Exon 6 of 8		NP_001257340.2
APOBEC3B-AS1	NR_104187.1	n.*152A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3B	ENST00000333467.4	c.799T>C	p.Leu267Leu	synonymous_variant	Exon 6 of 8	1	NM_004900.5	ENSP00000327459.3

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 250 AN: 146236 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00426

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000789

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000231

Gnomad SAS AF: 0.000227

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.000875

Gnomad OTH AF: 0.00152

GnomAD3 exomes AF: 0.000969 AC: 233 AN: 240558 Hom.: 4 AF XY: 0.000893 AC XY: 117 AN XY: 131072

Gnomad AFR exome AF: 0.00516

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.000125

Gnomad SAS exome AF: 0.000201

Gnomad FIN exome AF: 0.0000472

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.00143 AC: 2038 AN: 1426006 Hom.: 13 Cov.: 31 AF XY: 0.00139 AC XY: 988 AN XY: 710232

Gnomad4 AFR exome AF: 0.00520

Gnomad4 AMR exome AF: 0.000788

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000112

Gnomad4 SAS exome AF: 0.000155

Gnomad4 FIN exome AF: 0.0000378

Gnomad4 NFE exome AF: 0.00156

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00175 AC: 256 AN: 146312 Hom.: 0 Cov.: 30 AF XY: 0.00180 AC XY: 128 AN XY: 71084

Gnomad4 AFR AF: 0.00437

Gnomad4 AMR AF: 0.000789

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000232

Gnomad4 SAS AF: 0.000227

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000875

Gnomad4 OTH AF: 0.00152

Alfa AF: 0.000392 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.36

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: rs142595375; hg19: chr22-39387412;