9-121286186-G-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_198252.3(GSN):c.-10+4624G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,527,806 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 0.0010 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
GSN
NM_198252.3 intron
NM_198252.3 intron
Scores
1
4
Splicing: ADA: 0.01887
2
Clinical Significance
Conservation
PhyloP100: 1.19
Genes affected
GSN (HGNC:4620): (gelsolin) The protein encoded by this gene binds to the "plus" ends of actin monomers and filaments to prevent monomer exchange. The encoded calcium-regulated protein functions in both assembly and disassembly of actin filaments. Defects in this gene are a cause of familial amyloidosis Finnish type (FAF). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_addAF=-0.571344).
BP6
?
Variant 9-121286186-G-T is Benign according to our data. Variant chr9-121286186-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3040327.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00103 (157/152342) while in subpopulation AFR AF= 0.00354 (147/41572). AF 95% confidence interval is 0.00307. There are 0 homozygotes in gnomad4. There are 83 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 157 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSN | NM_198252.3 | c.-10+4624G>T | intron_variant | ENST00000432226.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSN | ENST00000432226.7 | c.-10+4624G>T | intron_variant | 5 | NM_198252.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00103 AC: 157AN: 152224Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000156 AC: 20AN: 128032Hom.: 0 AF XY: 0.000171 AC XY: 12AN XY: 70116
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GnomAD4 exome AF: 0.000108 AC: 148AN: 1375464Hom.: 0 Cov.: 28 AF XY: 0.0000869 AC XY: 59AN XY: 679204
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GSN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 01, 2021 | 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
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
FATHMM_MKL
Benign
N
MutationTaster
Benign
D;D;D;D;D;D;D
GERP RS
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at