rs3761857

Positions:

• chr9-121297774-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198252.3(GSN):​c.-9-4189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 152,098 control chromosomes in the GnomAD database, including 266 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (266 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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]

GSN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSN	NM_198252.3	c.-9-4189G>A		intron_variant		ENST00000432226.7	NP_937895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7	c.-9-4189G>A		intron_variant		5	NM_198252.3	ENSP00000404226.2

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4483 AN: 151980 Hom.: 264 Cov.: 33

Gnomad AFR AF: 0.00747

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00991

Gnomad OTH AF: 0.0277

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0295 AC: 4489 AN: 152098 Hom.: 266 Cov.: 33 AF XY: 0.0336 AC XY: 2498 AN XY: 74352

Gnomad4 AFR AF: 0.00745

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.00952

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.00993

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0158 Hom.: 19

Bravo AF: 0.0383

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.51

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: rs3761857; hg19: chr9-124060052;