chr9-121312976-G-A

Position:

• chr9-121312976-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.663+488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 156,520 control chromosomes in the GnomAD database, including 12,824 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 0.39 (12560 hom., cov: 32)
  • Exomes 𝑓: 0.34 (264 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.727

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSN	NM_198252.3	c.663+488G>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.663+488G>A		intron_variant		5	NM_198252.3	ENSP00000404226.2

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59666 AN: 151756 Hom.: 12550 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.337 AC: 1566 AN: 4646 Hom.: 264 Cov.: 0 AF XY: 0.340 AC XY: 825 AN XY: 2424

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.393 AC: 59711 AN: 151874 Hom.: 12560 Cov.: 32 AF XY: 0.390 AC XY: 28994 AN XY: 74258

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.343

Alfa AF: 0.243 Hom.: 560

Bravo AF: 0.402

Asia WGS AF: 0.308 AC: 1070 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	7.2
DANN	Benign	0.50

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: rs10818527; hg19: chr9-124075254;