rs4837820

Positions:

• chr9-121247816-G-A

Variant summary

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

The NM_001353053.1(GSN):​c.-460+16513G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,208 control chromosomes in the GnomAD database, including 13,503 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 (13503 hom., cov: 29)
• Consequence: GSN NM_001353053.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.97).
• 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	Protein	UniProt
GSN	NM_001353053.1	c.-460+16513G>A		intron_variant			NP_001339982.1
GSN	NM_001353054.1	c.-388-460G>A		intron_variant			NP_001339983.1
GSN	XM_047423267.1	c.-379+16513G>A		intron_variant			XP_047279223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000373823.7	c.-388-460G>A		intron_variant		5		ENSP00000362929.2
GSN	ENST00000434663.5	n.523+16513G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57171 AN: 151090 Hom.: 13489 Cov.: 29

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.378 AC: 57189 AN: 151208 Hom.: 13503 Cov.: 29 AF XY: 0.388 AC XY: 28577 AN XY: 73724

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.436

Alfa AF: 0.456 Hom.: 7900

Bravo AF: 0.357

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.4
DANN	Benign	0.64

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: rs4837820; hg19: chr9-124010094; COSMIC: COSV65743847;