9-121299557-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198252.3(GSN):c.-9-2406C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 789,000 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (514 hom., cov: 33)
  • Exomes 𝑓: 0.011 (181 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-121299557-C-T is Benign according to our data. Variant chr9-121299557-C-T is described in ClinVar as [Benign]. Clinvar id is 1283963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.-9-2406C>T		intron_variant		ENST00000432226.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.-9-2406C>T		intron_variant		5	NM_198252.3	P1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8828 AN: 152202 Hom.: 512 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0478

GnomAD4 exome AF: 0.0113 AC: 7196 AN: 636680 Hom.: 181 AF XY: 0.0113 AC XY: 3349 AN XY: 296708

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.0720

Gnomad4 FIN exome AF: 0.0243

Gnomad4 NFE exome AF: 0.00669

Gnomad4 OTH exome AF: 0.0276

GnomAD4 genome AF: 0.0581 AC: 8844 AN: 152320 Hom.: 514 Cov.: 33 AF XY: 0.0609 AC XY: 4538 AN XY: 74478

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0836

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0377 Hom.: 34

Bravo AF: 0.0712

Asia WGS AF: 0.100 AC: 347 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	9.9
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75473525; hg19: chr9-124061835;