chr21-43774195-G-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000100.4(CSTB):c.*7C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,614,226 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 2 hom. )
Consequence
CSTB
NM_000100.4 3_prime_UTR
NM_000100.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.04
Genes affected
CSTB (HGNC:2482): (cystatin B) The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and kininogens. This gene encodes a stefin that functions as an intracellular thiol protease inhibitor. The protein is able to form a dimer stabilized by noncovalent forces, inhibiting papain and cathepsins l, h and b. The protein is thought to play a role in protecting against the proteases leaking from lysosomes. Evidence indicates that mutations in this gene are responsible for the primary defects in patients with progressive myoclonic epilepsy (EPM1). One type of mutation responsible for EPM1 is the expansion in the promoter region of this gene of a CCCCGCCCCGCG repeat from 2-3 copies to 30-78 copies. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 21-43774195-G-C is Benign according to our data. Variant chr21-43774195-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 377757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00143 (218/152352) while in subpopulation AFR AF= 0.00508 (211/41570). AF 95% confidence interval is 0.00451. There are 2 homozygotes in gnomad4. There are 103 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSTB | NM_000100.4 | c.*7C>G | 3_prime_UTR_variant | 3/3 | ENST00000291568.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSTB | ENST00000291568.7 | c.*7C>G | 3_prime_UTR_variant | 3/3 | 1 | NM_000100.4 | P1 | ||
CSTB | ENST00000639959.1 | c.*7C>G | 3_prime_UTR_variant | 2/2 | 5 | ||||
CSTB | ENST00000640406.1 | c.*379C>G | 3_prime_UTR_variant | 2/2 | 2 | ||||
CSTB | ENST00000675996.1 | n.729C>G | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes AF: 0.00142 AC: 216AN: 152234Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000378 AC: 95AN: 251464Hom.: 1 AF XY: 0.000287 AC XY: 39AN XY: 135920
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GnomAD4 exome AF: 0.000145 AC: 212AN: 1461874Hom.: 2 Cov.: 31 AF XY: 0.000135 AC XY: 98AN XY: 727244
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GnomAD4 genome AF: 0.00143 AC: 218AN: 152352Hom.: 2 Cov.: 33 AF XY: 0.00138 AC XY: 103AN XY: 74500
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 15, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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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