chr19-50906943-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_004917.5(KLK4):c.756G>A(p.Gln252=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )
Consequence
KLK4
NM_004917.5 synonymous
NM_004917.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.256
Genes affected
KLK4 (HGNC:6365): (kallikrein related peptidase 4) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 19-50906943-C-T is Benign according to our data. Variant chr19-50906943-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.256 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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KLK4 | NM_004917.5 | c.756G>A | p.Gln252= | synonymous_variant | 6/6 | ENST00000324041.6 | |
KLK4 | NM_001302961.2 | c.471G>A | p.Gln157= | synonymous_variant | 5/5 | ||
KLK4 | NR_126566.2 | n.745G>A | non_coding_transcript_exon_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLK4 | ENST00000324041.6 | c.756G>A | p.Gln252= | synonymous_variant | 6/6 | 1 | NM_004917.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152132Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251492Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135920
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GnomAD4 exome AF: 0.000242 AC: 354AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.000231 AC XY: 168AN XY: 727246
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74310
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | KLK4: BP4, BP7 - |
KLK4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at