9-121235267-G-A

Position:

• chr9-121235267-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+3964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 152,282 control chromosomes in the GnomAD database, including 458 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 0.054 (458 hom., cov: 32)
• Consequence: GSN NM_001353053.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSN	NM_001353053.1	c.-460+3964G>A		intron_variant			NP_001339982.1
GSN	NM_001353054.1	c.-389+3964G>A		intron_variant			NP_001339983.1
GSN	XM_047423267.1	c.-379+3964G>A		intron_variant			XP_047279223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000373823.7	c.-389+3964G>A		intron_variant		5		ENSP00000362929.2
GSN	ENST00000434663.5	n.523+3964G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8162 AN: 152164 Hom.: 453 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0489

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

GnomAD4 genome AF: 0.0537 AC: 8179 AN: 152282 Hom.: 458 Cov.: 32 AF XY: 0.0571 AC XY: 4252 AN XY: 74458

Gnomad4 AFR AF: 0.0889

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0837

Gnomad4 FIN AF: 0.0280

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0484

Alfa AF: 0.0340 Hom.: 30

Bravo AF: 0.0669

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.71

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: rs10513362; hg19: chr9-123997545;