9-121270766-C-A

Variant names:

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

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: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198252.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	NM_198252.3	MANE Select	c.-103+2547C>A		intron	N/A	NP_937895.1	P06396-2
	GSN	NM_001127663.2		c.-107+2547C>A		intron	N/A	NP_001121135.2	A0A0A0MT01
	GSN	NM_001353076.2		c.-141+2547C>A		intron	N/A	NP_001340005.1	A0A8V8TND7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	ENST00000432226.7	TSL:5 MANE Select	c.-103+2547C>A		intron	N/A	ENSP00000404226.2	P06396-2
	GSN	ENST00000900575.1		c.-103+2547C>A		intron	N/A	ENSP00000570634.1
	GSN	ENST00000449733.7	TSL:2	c.-107+2547C>A		intron	N/A	ENSP00000409358.2	A0A0A0MT01

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 v4.9

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;