dbSNP rs7046030: GSN:c.-10+3397T>C (chr9-121284959-T-C) – 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.-10+3397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 167,134 control chromosomes in the GnomAD database, including 4,767 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 0.23 ( 4525 hom., cov: 32)

Exomes 𝑓: 0.18 ( 242 hom. )

Consequence

GSN
NM_198252.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.301

Publications

8 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 links:

GSN-AS1 (HGNC:23372): (GSN antisense RNA 1)

GSN-AS1 links:

ENSG00000239593 (HGNC:):

ENSG00000239593 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 (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_198252.3 link	c.-10+3397T>C		intron_variant	Intron 2 of 17	ENST00000432226.7	NP_937895.1	P06396-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7 link	c.-10+3397T>C		intron_variant	Intron 2 of 17	5	NM_198252.3	ENSP00000404226.2		P06396-2Q5T0I0

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34304

AN:

151854

Hom.:

4520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.0538

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.173

GnomAD4 exome

AF:

0.178

AC:

2691

AN:

15160

Hom.:

242

Cov.:

AF XY:

0.174

AC XY:

1259

AN XY:

7242

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.177

AC:

2614

AN:

14784

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.199

AC:

AN:

236

Other (OTH)

AF:

0.226

AC:

AN:

106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

151

302

454

605

756

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:

0.226

AC:

34333

AN:

151974

Hom.:

4525

Cov.:

AF XY:

0.221

AC XY:

16421

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.365

AC:

15117

AN:

41388

American (AMR)

AF:

0.147

AC:

2239

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

348

AN:

3472

East Asian (EAS)

AF:

0.0534

AC:

276

AN:

5172

South Asian (SAS)

AF:

0.123

AC:

595

AN:

4818

European-Finnish (FIN)

AF:

0.183

AC:

1937

AN:

10578

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.196

AC:

13311

AN:

67952

Other (OTH)

AF:

0.173

AC:

366

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1317

2634

3950

5267

6584

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.201

Hom.:

8835

Bravo

AF:

0.226

Asia WGS

AF:

0.126

AC:

439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

(source)

DANN

Benign

0.50

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over