rs4837839

Positions:

• chr9-121309849-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.352-835C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,956 control chromosomes in the GnomAD database, including 12,450 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 0.36 (12432 hom., cov: 31)
  • Exomes 𝑓: 0.49 (18 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.352-835C>T		intron_variant		ENST00000432226.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.352-835C>T		intron_variant		5	NM_198252.3	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54959 AN: 151702 Hom.: 12420 Cov.: 31

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.493 AC: 67 AN: 136 Hom.: 18 Cov.: 0 AF XY: 0.509 AC XY: 57 AN XY: 112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.362 AC: 54975 AN: 151820 Hom.: 12432 Cov.: 31 AF XY: 0.371 AC XY: 27506 AN XY: 74168

Gnomad4 AFR AF: 0.0844

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.426

Alfa AF: 0.396 Hom.: 1721

Bravo AF: 0.340

Asia WGS AF: 0.492 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.28

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: rs4837839; hg19: chr9-124072127; COSMIC: COSV57996356; COSMIC: COSV57996356;