chr1-6601921-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_014851.4(KLHL21):c.897C>T(p.Asp299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,562,822 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.012 ( 31 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 27 hom. )
Consequence
KLHL21
NM_014851.4 synonymous
NM_014851.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.131
Genes affected
KLHL21 (HGNC:29041): (kelch like family member 21) Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in polar microtubule. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 1-6601921-G-A is Benign according to our data. Variant chr1-6601921-G-A is described in ClinVar as [Benign]. Clinvar id is 3034671.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.131 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1782/152352) while in subpopulation AFR AF= 0.0407 (1692/41582). AF 95% confidence interval is 0.0391. There are 31 homozygotes in gnomad4. There are 843 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 31 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL21 | NM_014851.4 | c.897C>T | p.Asp299= | synonymous_variant | 1/4 | ENST00000377658.8 | |
KLHL21 | NM_001324309.2 | c.897C>T | p.Asp299= | synonymous_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL21 | ENST00000377658.8 | c.897C>T | p.Asp299= | synonymous_variant | 1/4 | 1 | NM_014851.4 | P1 | |
KLHL21 | ENST00000377663.3 | c.897C>T | p.Asp299= | synonymous_variant | 1/3 | 1 | |||
KLHL21 | ENST00000463043.1 | c.-80-2469C>T | intron_variant | 5 | |||||
KLHL21 | ENST00000467612.5 | c.-80-2469C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0117 AC: 1782AN: 152234Hom.: 31 Cov.: 33
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GnomAD3 exomes AF: 0.00297 AC: 504AN: 169440Hom.: 9 AF XY: 0.00223 AC XY: 202AN XY: 90572
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GnomAD4 exome AF: 0.00118 AC: 1665AN: 1410470Hom.: 27 Cov.: 32 AF XY: 0.00101 AC XY: 703AN XY: 697086
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GnomAD4 genome AF: 0.0117 AC: 1782AN: 152352Hom.: 31 Cov.: 33 AF XY: 0.0113 AC XY: 843AN XY: 74502
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KLHL21-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 13, 2019 | This variant is classified as 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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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at