rs3733402
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000892.5(KLKB1):c.428G>A(p.Ser143Asn) variant causes a missense change. The variant allele was found at a frequency of 0.524 in 1,613,244 control chromosomes in the GnomAD database, including 226,077 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000892.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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KLKB1 | ENST00000264690.11 | c.428G>A | p.Ser143Asn | missense_variant | Exon 5 of 15 | 1 | NM_000892.5 | ENSP00000264690.6 | ||
ENSG00000290316 | ENST00000511608.5 | c.569G>A | p.Ser190Asn | missense_variant | Exon 5 of 15 | 5 | ENSP00000426629.1 |
Frequencies
GnomAD3 genomes AF: 0.587 AC: 89168AN: 151810Hom.: 27042 Cov.: 30
GnomAD3 exomes AF: 0.540 AC: 135782AN: 251352Hom.: 37996 AF XY: 0.525 AC XY: 71298AN XY: 135838
GnomAD4 exome AF: 0.518 AC: 756256AN: 1461314Hom.: 198983 Cov.: 43 AF XY: 0.512 AC XY: 371965AN XY: 726952
GnomAD4 genome AF: 0.588 AC: 89276AN: 151930Hom.: 27094 Cov.: 30 AF XY: 0.587 AC XY: 43554AN XY: 74240
ClinVar
Submissions by phenotype
not specified Benign:3
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While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.729, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -
Prekallikrein deficiency Pathogenic:1Benign:1
NM_000892.3:c.428G>A (Ser143Asn) in the KLKB1 gene has an allele frequency of 0.738 in African subpopulation in the gnomAD database, including 43762 homozygous events. Ser143Asn was reported as N124S according to ClinVar's annotation. Katsuda et al reported three Japanese patients with plasma prekallikrein deficiency, who harbors homozygousity of Gly104Arg and Asn124Ser in 2007. Co-segregate analysis demonstrate the proband's parents were heterozygous of Gly104Arg Asn124-Ser\Gly104Arg+ (PMID: 17598838). Considering the high frequency of this variant, we classify the variant as benign. ACMG/AMP criteria applied: BA1, BS2. -
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not provided Benign:2
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This variant is associated with the following publications: (PMID: 20981092, 24625756, 23251661, 17598838, 28508493, 28492530) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at