9-121299685-G-A

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.-9-2278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 778,732 control chromosomes in the GnomAD database, including 17,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4532 hom., cov: 32)
  • Exomes 𝑓: 0.19 (12485 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.288

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=-0.72).
• BP6: Variant 9-121299685-G-A is Benign according to our data. Variant chr9-121299685-G-A is described in ClinVar as [Benign]. Clinvar id is 1255271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.-9-2278G>A		intron_variant		ENST00000432226.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.-9-2278G>A		intron_variant		5	NM_198252.3	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34326 AN: 151968 Hom.: 4527 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0536

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.192 AC: 120562 AN: 626644 Hom.: 12485 AF XY: 0.192 AC XY: 58041 AN XY: 301746

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0598

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.226 AC: 34355 AN: 152088 Hom.: 4532 Cov.: 32 AF XY: 0.221 AC XY: 16444 AN XY: 74368

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.175

Alfa AF: 0.224 Hom.: 516

Bravo AF: 0.226

Asia WGS AF: 0.125 AC: 436 AN: 3478

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	-0.72
Cadd	Benign	6.6
Dann	Benign	0.94

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: rs6478506; hg19: chr9-124061963;