rs12683989

Variant names:

• chr9-121323768-C-T
• rs12683989
• NM_198252.3:c.1326-786C>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.1326-786C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,172 control chromosomes in the GnomAD database, including 424 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 0.067 (424 hom., cov: 32)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_198252.3	c.1326-786C>T		intron_variant	Intron 11 of 17	ENST00000432226.7	NP_937895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7	c.1326-786C>T		intron_variant	Intron 11 of 17	5	NM_198252.3	ENSP00000404226.2

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10209 AN: 152054 Hom.: 422 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0566

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

GnomAD4 genome AF: 0.0671 AC: 10204 AN: 152172 Hom.: 424 Cov.: 32 AF XY: 0.0649 AC XY: 4826 AN XY: 74412

African (AFR) AF: 0.112 AC: 4636 AN: 41494

American (AMR) AF: 0.0421 AC: 644 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3472

East Asian (EAS) AF: 0.0429 AC: 222 AN: 5178

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4822

European-Finnish (FIN) AF: 0.0270 AC: 286 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4015 AN: 68004

Other (OTH) AF: 0.0560 AC: 118 AN: 2106

Alfa AF: 0.0633 Hom.: 294

Bravo AF: 0.0697

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.37
PhyloP100		-0.97
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: rs12683989; hg19: chr9-124086046;