dbSNP rs4837839: GSN:c.352-835C>T (chr9-121309849-C-T) – 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.352-835C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,956 control chromosomes in the GnomAD database, including 12,450 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 0.36 ( 12432 hom., cov: 31)

Exomes 𝑓: 0.49 ( 18 hom. )

Consequence

GSN
NM_198252.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.303

Publications

5 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: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, 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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 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	UniProt
GSN	NM_198252.3	MANE Select	c.352-835C>T	intron	N/A	NP_937895.1	P06396-2
GSN	NM_000177.5		c.505-835C>T	intron	N/A	NP_000168.1	P06396-1
GSN	NM_001127663.2		c.460-835C>T	intron	N/A	NP_001121135.2	A0A0A0MT01

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSN	ENST00000432226.7	TSL:5 MANE Select	c.352-835C>T	intron	N/A	ENSP00000404226.2	P06396-2
GSN	ENST00000373818.8	TSL:1	c.505-835C>T	intron	N/A	ENSP00000362924.4	P06396-1
GSN	ENST00000485767.1	TSL:1	n.1479C>T	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54959

AN:

151702

Hom.:

12420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0845

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.509

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.493

AC:

AN:

136

Hom.:

Cov.:

AF XY:

0.509

AC XY:

AN XY:

112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.519

AC:

AN:

108

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.362

AC:

54975

AN:

151820

Hom.:

12432

Cov.:

AF XY:

0.371

AC XY:

27506

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.0844

AC:

3498

AN:

41430

American (AMR)

AF:

0.423

AC:

6449

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

1509

AN:

3464

East Asian (EAS)

AF:

0.508

AC:

2612

AN:

5138

South Asian (SAS)

AF:

0.590

AC:

2825

AN:

4792

European-Finnish (FIN)

AF:

0.542

AC:

5700

AN:

10512

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.454

AC:

30809

AN:

67918

Other (OTH)

AF:

0.426

AC:

897

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1523

3047

4570

6094

7617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.396

Hom.:

1721

Bravo

AF:

0.340

Asia WGS

AF:

0.492

AC:

1712

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.4

(source)

DANN

Benign

0.28

PhyloP100

0.30

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over