rs10818524

Variant names:

• chr9-121267901-T-C
• rs10818524
• NM_001353053.1:c.-103+376T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-121267901-T-C
• chr9-121267901-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353053.1(GSN):​c.-103+376T>C 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 152,042 control chromosomes in the GnomAD database, including 13,513 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 (13513 hom., cov: 32)
• Consequence: GSN NM_001353053.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_001353053.1	c.-103+376T>C		intron_variant	Intron 9 of 25		NP_001339982.1
GSN	NM_001353054.1	c.-103+2147T>C		intron_variant	Intron 9 of 25		NP_001339983.1
GSN	XM_047423267.1	c.-141+2147T>C		intron_variant	Intron 8 of 25		XP_047279223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000373823.7	c.-103+2147T>C		intron_variant	Intron 8 of 24	5		ENSP00000362929.2
GSN	ENST00000373808.8	c.-459T>C		upstream_gene_variant		2		ENSP00000362914.3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57430 AN: 151924 Hom.: 13501 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.560

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: 0.378 AC: 57448 AN: 152042 Hom.: 13513 Cov.: 32 AF XY: 0.388 AC XY: 28806 AN XY: 74308

African (AFR) AF: 0.0891 AC: 3701 AN: 41530

American (AMR) AF: 0.448 AC: 6859 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3468

East Asian (EAS) AF: 0.602 AC: 3096 AN: 5144

South Asian (SAS) AF: 0.601 AC: 2897 AN: 4818

European-Finnish (FIN) AF: 0.560 AC: 5909 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31805 AN: 67914

Other (OTH) AF: 0.435 AC: 919 AN: 2112

Alfa AF: 0.444 Hom.: 22219

Bravo AF: 0.356

Asia WGS AF: 0.540 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.40
PromoterAI		-0.050	Neutral
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: rs10818524; hg19: chr9-124030179; COSMIC: COSV57995926; COSMIC: COSV57995926;