rs306784

chr9-121310374-G-T

Variant summary

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

The NM_198252.3(GSN):c.352-310G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 409,426 control chromosomes in the GnomAD database, including 29,444 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 (14342 hom., cov: 32)
  • Exomes 𝑓: 0.33 (15102 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.352-310G>T		intron_variant		ENST00000432226.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.352-310G>T		intron_variant		5	NM_198252.3	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62161 AN: 151858 Hom.: 14330 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.328 AC: 84356 AN: 257450 Hom.: 15102 Cov.: 0 AF XY: 0.317 AC XY: 43820 AN XY: 138094

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.409 AC: 62207 AN: 151976 Hom.: 14342 Cov.: 32 AF XY: 0.400 AC XY: 29739 AN XY: 74284

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.363

Alfa AF: 0.371 Hom.: 15143

Bravo AF: 0.411

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.0
Dann	Benign	0.48

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: rs306784; hg19: chr9-124072652;