rs10985196

Variant names:

• chr9-121270766-C-A
• rs10985196
• NM_198252.3:c.-103+2547C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-121270766-C-A
• chr9-121270766-C-T

Variant summary

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

The NM_198252.3(GSN):​c.-103+2547C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,030 control chromosomes in the GnomAD database, including 7,000 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 0.28 (7000 hom., cov: 32)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857
• Publications: 9 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_198252.3	c.-103+2547C>A		intron_variant	Intron 1 of 17	ENST00000432226.7	NP_937895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7	c.-103+2547C>A		intron_variant	Intron 1 of 17	5	NM_198252.3	ENSP00000404226.2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42535 AN: 151910 Hom.: 6985 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.280 AC: 42583 AN: 152030 Hom.: 7000 Cov.: 32 AF XY: 0.279 AC XY: 20701 AN XY: 74298

African (AFR) AF: 0.457 AC: 18936 AN: 41422

American (AMR) AF: 0.288 AC: 4408 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1064 AN: 5168

South Asian (SAS) AF: 0.207 AC: 996 AN: 4820

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10558

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 13984 AN: 67996

Other (OTH) AF: 0.222 AC: 470 AN: 2114

Alfa AF: 0.218 Hom.: 5087

Bravo AF: 0.293

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.71
PhyloP100		0.86
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: rs10985196; hg19: chr9-124033044;