22-38985899-A-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_004900.5(APOBEC3B):āc.262A>Cā(p.Ile88Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,599,610 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Consequence
NM_004900.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOBEC3B | ENST00000333467.4 | c.262A>C | p.Ile88Leu | missense_variant | Exon 3 of 8 | 1 | NM_004900.5 | ENSP00000327459.3 | ||
APOBEC3B | ENST00000407298.7 | c.262A>C | p.Ile88Leu | missense_variant | Exon 3 of 8 | 1 | ENSP00000385068.3 | |||
APOBEC3B | ENST00000335760.9 | n.262A>C | non_coding_transcript_exon_variant | Exon 3 of 7 | 1 | ENSP00000338897.5 | ||||
APOBEC3B | ENST00000402182.7 | c.262A>C | p.Ile88Leu | missense_variant | Exon 3 of 7 | 2 | ENSP00000385060.3 |
Frequencies
GnomAD3 genomes AF: 0.00745 AC: 1099AN: 147516Hom.: 56 Cov.: 28
GnomAD3 exomes AF: 0.00211 AC: 526AN: 248810Hom.: 16 AF XY: 0.00155 AC XY: 208AN XY: 134608
GnomAD4 exome AF: 0.000720 AC: 1045AN: 1452022Hom.: 41 Cov.: 81 AF XY: 0.000631 AC XY: 456AN XY: 722300
GnomAD4 genome AF: 0.00745 AC: 1100AN: 147588Hom.: 55 Cov.: 28 AF XY: 0.00698 AC XY: 501AN XY: 71760
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The APOBEC3B p.Ile88Leu variant was not identified in the literature nor was it identified in ClinVar or Cosmic. The variant was identified in dbSNP (ID: rs151303359) and LOVD 3.0. The variant was identified in control databases in 759 of 279140 chromosomes (28 homozygous) at a frequency of 0.002719 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 680 of 24728 chromosomes (freq: 0.0275), Latino in 50 of 34640 chromosomes (freq: 0.001443), Other in 10 of 7134 chromosomes (freq: 0.001402) and European (non-Finnish) in 19 of 128516 chromosomes (freq: 0.000148), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.Ile88 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at