rs306783

Positions:

• chr9-121310319-C-T

Variant summary

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

The NM_198252.3(GSN):​c.352-365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 334,032 control chromosomes in the GnomAD database, including 28,035 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 0.41 (13422 hom., cov: 31)
  • Exomes 𝑓: 0.39 (14613 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.352-365C>T		intron_variant		ENST00000432226.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.352-365C>T		intron_variant		5	NM_198252.3	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62779 AN: 151816 Hom.: 13426 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.389 AC: 70838 AN: 182098 Hom.: 14613 Cov.: 0 AF XY: 0.383 AC XY: 37693 AN XY: 98538

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.413 AC: 62802 AN: 151934 Hom.: 13422 Cov.: 31 AF XY: 0.406 AC XY: 30160 AN XY: 74254

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.389

Alfa AF: 0.421 Hom.: 6536

Bravo AF: 0.407

Asia WGS AF: 0.262 AC: 914 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	7.8
DANN	Benign	0.81

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: rs306783; hg19: chr9-124072597;