chr9-121277593-C-T

Variant names:

• chr9-121277593-C-T
• rs4837827
• NM_198252.3:c.-102-3877C>T

Variant summary

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

The NM_001127663.2(GSN):​c.-106-3877C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,980 control chromosomes in the GnomAD database, including 13,579 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 (13579 hom., cov: 33)
• Consequence: GSN NM_001127663.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127663.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	NM_198252.3	MANE Select	c.-102-3877C>T		intron	N/A	NP_937895.1
	GSN	NM_001127663.2		c.-106-3877C>T		intron	N/A	NP_001121135.2
	GSN	NM_001353076.2		c.-140-3877C>T		intron	N/A	NP_001340005.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	ENST00000432226.7	TSL:5 MANE Select	c.-102-3877C>T		intron	N/A	ENSP00000404226.2
	GSN	ENST00000900575.1		c.-102-3877C>T		intron	N/A	ENSP00000570634.1
	GSN	ENST00000449733.7	TSL:2	c.-106-3877C>T		intron	N/A	ENSP00000409358.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57519 AN: 151862 Hom.: 13567 Cov.: 33

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.561

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: 0.379 AC: 57537 AN: 151980 Hom.: 13579 Cov.: 33 AF XY: 0.389 AC XY: 28866 AN XY: 74272

African (AFR) AF: 0.0893 AC: 3707 AN: 41524

American (AMR) AF: 0.449 AC: 6829 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3198 AN: 5148

South Asian (SAS) AF: 0.603 AC: 2904 AN: 4814

European-Finnish (FIN) AF: 0.561 AC: 5918 AN: 10552

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

European-Non Finnish (NFE) AF: 0.468 AC: 31805 AN: 67958

Other (OTH) AF: 0.436 AC: 921 AN: 2114

Alfa AF: 0.436 Hom.: 4085

Bravo AF: 0.357

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.32
PhyloP100		0.067
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: rs4837827; hg19: chr9-124039871;