dbSNP rs10818527: GSN:c.663+488G>A (chr9-121312976-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.663+488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 156,520 control chromosomes in the GnomAD database, including 12,824 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 0.39 ( 12560 hom., cov: 32)

Exomes 𝑓: 0.34 ( 264 hom. )

Consequence

GSN
NM_198252.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.727

Publications

4 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 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.663+488G>A	intron	N/A	NP_937895.1	P06396-2
GSN	NM_000177.5		c.816+488G>A	intron	N/A	NP_000168.1	P06396-1
GSN	NM_001127663.2		c.771+488G>A	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.663+488G>A	intron	N/A	ENSP00000404226.2	P06396-2
GSN	ENST00000373818.8	TSL:1	c.816+488G>A	intron	N/A	ENSP00000362924.4	P06396-1
GSN	ENST00000485767.1	TSL:1	n.4606G>A	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59666

AN:

151756

Hom.:

12550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.342

GnomAD4 exome

AF:

0.337

AC:

1566

AN:

4646

Hom.:

264

Cov.:

AF XY:

0.340

AC XY:

825

AN XY:

2424

show subpopulations

African (AFR)

AF:

0.545

AC:

AN:

American (AMR)

AF:

0.429

AC:

364

AN:

848

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

AN:

East Asian (EAS)

AF:

0.294

AC:

AN:

102

South Asian (SAS)

AF:

0.266

AC:

107

AN:

402

European-Finnish (FIN)

AF:

0.293

AC:

AN:

Middle Eastern (MID)

AF:

0.400

AC:

AN:

European-Non Finnish (NFE)

AF:

0.317

AC:

942

AN:

2976

Other (OTH)

AF:

0.411

AC:

AN:

202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.393

AC:

59711

AN:

151874

Hom.:

12560

Cov.:

AF XY:

0.390

AC XY:

28994

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.549

AC:

22718

AN:

41400

American (AMR)

AF:

0.377

AC:

5755

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

928

AN:

3468

East Asian (EAS)

AF:

0.249

AC:

1285

AN:

5162

South Asian (SAS)

AF:

0.263

AC:

1268

AN:

4824

European-Finnish (FIN)

AF:

0.348

AC:

3676

AN:

10552

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23042

AN:

67894

Other (OTH)

AF:

0.343

AC:

722

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1794

3589

5383

7178

8972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.261

Hom.:

673

Bravo

AF:

0.402

Asia WGS

AF:

0.308

AC:

1070

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.2

(source)

DANN

Benign

0.50

PhyloP100

0.73

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