rs4837827

Positions:

• chr9-121277593-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.-102-3877C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,980 control chromosomes in the GnomAD database, including 13,579 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 0.38 (13579 hom., cov: 33)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.-102-3877C>T		intron_variant		ENST00000432226.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.-102-3877C>T		intron_variant		5	NM_198252.3	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57519 AN: 151862 Hom.: 13567 Cov.: 33

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 57537 AN: 151980 Hom.: 13579 Cov.: 33 AF XY: 0.389 AC XY: 28866 AN XY: 74272

Gnomad4 AFR AF: 0.0893

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.436

Alfa AF: 0.442 Hom.: 4072

Bravo AF: 0.357

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.32

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: rs4837827; hg19: chr9-124039871;