chr9-121282470-C-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+908C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,267,542 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00038 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00035 ( 2 hom. )
Consequence
GSN
NM_198252.3 intron
NM_198252.3 intron
Scores
8
Clinical Significance
Conservation
PhyloP100: -0.0570
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 (MetaRNN=0.040370256).
BP6
?
Variant 9-121282470-C-T is Benign according to our data. Variant chr9-121282470-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3058775.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000381 (58/152316) while in subpopulation SAS AF= 0.000622 (3/4826). AF 95% confidence interval is 0.000292. There are 1 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 58 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSN | NM_198252.3 | c.-10+908C>T | intron_variant | ENST00000432226.7 | |||
GSN-AS1 | NR_103560.1 | n.3061G>A | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSN | ENST00000432226.7 | c.-10+908C>T | intron_variant | 5 | NM_198252.3 | P1 | |||
GSN-AS1 | ENST00000414544.1 | n.3061G>A | non_coding_transcript_exon_variant | 1/1 | |||||
ENST00000437135.1 | n.261G>A | splice_region_variant, non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000381 AC: 58AN: 152198Hom.: 1 Cov.: 33
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GnomAD4 exome AF: 0.000352 AC: 393AN: 1115226Hom.: 2 Cov.: 28 AF XY: 0.000349 AC XY: 184AN XY: 527884
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GnomAD4 genome ? AF: 0.000381 AC: 58AN: 152316Hom.: 1 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74470
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3478
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 09, 2022 | 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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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N
Vest4
MVP
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Splicing
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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