rs10513362

Variant names:

• chr9-121235267-G-A
• rs10513362
• NM_001353053.1:c.-460+3964G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Finnish type amyloidosis

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GSN	NM_001353053.1	c.-460+3964G>A		intron_variant	Intron 6 of 25		NP_001339982.1
GSN	NM_001353054.1	c.-389+3964G>A		intron_variant	Intron 6 of 25		NP_001339983.1
GSN	XM_047423267.1	c.-379+3964G>A		intron_variant	Intron 6 of 25		XP_047279223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000373823.7	c.-389+3964G>A		intron_variant	Intron 5 of 24	5		ENSP00000362929.2
GSN	ENST00000434663.5	n.523+3964G>A		intron_variant	Intron 5 of 5	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

African (AFR) AF: 0.0889 AC: 3694 AN: 41550

American (AMR) AF: 0.145 AC: 2212 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.134 AC: 696 AN: 5178

South Asian (SAS) AF: 0.0837 AC: 404 AN: 4828

European-Finnish (FIN) AF: 0.0280 AC: 297 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 736 AN: 68034

Other (OTH) AF: 0.0484 AC: 102 AN: 2106

Alfa AF: 0.0218 Hom.: 156

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
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10513362; hg19: chr9-123997545;