22-38991407-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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]

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

ACMG classification

Our verdict: Benign. The variant received -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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270411.2. 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.799T>C	p.Leu267Leu	synonymous	Exon 6 of 8	NP_004891.5
	APOBEC3B	NM_001270411.2		c.724T>C	p.Leu242Leu	splice_region synonymous	Exon 6 of 8	NP_001257340.2	Q9UH17-3
	APOBEC3B-AS1	NR_104187.1		n.*152A>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3B	ENST00000333467.4	TSL:1 MANE Select	c.799T>C	p.Leu267Leu	synonymous	Exon 6 of 8	ENSP00000327459.3	Q9UH17-1
	APOBEC3B	ENST00000407298.7	TSL:1	c.724T>C	p.Leu242Leu	splice_region synonymous	Exon 6 of 8	ENSP00000385068.3	Q9UH17-3
	APOBEC3B	ENST00000335760.9	TSL:1	n.645T>C		non_coding_transcript_exon	Exon 5 of 7	ENSP00000338897.5	Q9UH17-2

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

GnomAD2 exomes AF: 0.000969 AC: 233 AN: 240558 AF XY: 0.000893

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00520 AC: 173 AN: 33270

American (AMR) AF: 0.000788 AC: 33 AN: 41876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.000112 AC: 4 AN: 35820

South Asian (SAS) AF: 0.000155 AC: 13 AN: 83824

European-Finnish (FIN) AF: 0.0000378 AC: 2 AN: 52914

Middle Eastern (MID) AF: 0.00158 AC: 8 AN: 5072

European-Non Finnish (NFE) AF: 0.00156 AC: 1700 AN: 1088540

Other (OTH) AF: 0.00179 AC: 105 AN: 58720

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00437 AC: 178 AN: 40762

American (AMR) AF: 0.000789 AC: 11 AN: 13940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.000232 AC: 1 AN: 4306

South Asian (SAS) AF: 0.000227 AC: 1 AN: 4396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10084

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000875 AC: 58 AN: 66306

Other (OTH) AF: 0.00152 AC: 3 AN: 1968

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000392 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.36
PhyloP100		-0.0090
Mutation Taster		=93/7	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: rs142595375; hg19: chr22-39387412;