chr9-121330077-C-T

Variant names:

• chr9-121330077-C-T
• rs306772
• NM_198252.3:c.1965+762C>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.1965+762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,036 control chromosomes in the GnomAD database, including 5,114 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 0.24 (5114 hom., cov: 32)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 17 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 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.1965+762C>T		intron	N/A	NP_937895.1
	GSN	NM_000177.5		c.2118+762C>T		intron	N/A	NP_000168.1
	GSN	NM_001127663.2		c.2073+762C>T		intron	N/A	NP_001121135.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	ENST00000432226.7	TSL:5 MANE Select	c.1965+762C>T		intron	N/A	ENSP00000404226.2
	GSN	ENST00000373818.8	TSL:1	c.2118+762C>T		intron	N/A	ENSP00000362924.4
	GSN	ENST00000900575.1		c.2124+762C>T		intron	N/A	ENSP00000570634.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36290 AN: 151918 Hom.: 5111 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.239 AC: 36319 AN: 152036 Hom.: 5114 Cov.: 32 AF XY: 0.234 AC XY: 17382 AN XY: 74304

African (AFR) AF: 0.394 AC: 16313 AN: 41430

American (AMR) AF: 0.133 AC: 2038 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.104 AC: 538 AN: 5170

South Asian (SAS) AF: 0.124 AC: 596 AN: 4824

European-Finnish (FIN) AF: 0.208 AC: 2197 AN: 10568

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13759 AN: 67972

Other (OTH) AF: 0.185 AC: 391 AN: 2114

Alfa AF: 0.207 Hom.: 12794

Bravo AF: 0.237

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Benign	0.81
PhyloP100		-0.19
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: rs306772; hg19: chr9-124092355;