dbSNP rs3761857: GSN:c.-9-4189G>A (chr9-121297774-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198252.3(GSN):c.-9-4189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 152,098 control chromosomes in the GnomAD database, including 266 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 0.030 ( 266 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GSN
NM_198252.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.193

Publications

1 publications found

Variant links:

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)

GSN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSN	NM_198252.3	MANE Select	c.-9-4189G>A	intron	N/A	NP_937895.1
GSN	NM_001127663.2		c.100-4189G>A	intron	N/A	NP_001121135.2
GSN	NM_001353076.2		c.-47-2282G>A	intron	N/A	NP_001340005.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSN	ENST00000432226.7	TSL:5 MANE Select	c.-9-4189G>A	intron	N/A	ENSP00000404226.2
GSN	ENST00000483960.5	TSL:3	n.286G>A	non_coding_transcript_exon	Exon 4 of 8
GSN	ENST00000449733.7	TSL:2	c.100-4189G>A	intron	N/A	ENSP00000409358.2

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4483

AN:

151980

Hom.:

264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00747

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.0828

Gnomad FIN

AF:

0.0279

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00991

Gnomad OTH

AF:

0.0277

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0295

AC:

4489

AN:

152098

Hom.:

266

Cov.:

AF XY:

0.0336

AC XY:

2498

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00745

AC:

309

AN:

41498

American (AMR)

AF:

0.132

AC:

2021

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00952

AC:

AN:

3468

East Asian (EAS)

AF:

0.135

AC:

697

AN:

5170

South Asian (SAS)

AF:

0.0831

AC:

400

AN:

4812

European-Finnish (FIN)

AF:

0.0279

AC:

295

AN:

10576

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00993

AC:

675

AN:

67988

Other (OTH)

AF:

0.0274

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

193

385

578

770

963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0145

Hom.:

Bravo

AF:

0.0383

Asia WGS

AF:

0.0940

AC:

324

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.8

(source)

DANN

Benign

0.51

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over