Genetic Variant GSN:c.-10+1754delT (chr9-121283301-CT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001353074.2(GSN):c.-121-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10874 hom., cov: 0)

Exomes 𝑓: 0.39 ( 113 hom. )

Consequence

GSN
NM_001353074.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.469

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 links:

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

GSN-AS1 links:

ENSG00000239593 (HGNC:):

ENSG00000239593 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353074.2. 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.-10+1754delT	intron	N/A	NP_937895.1	P06396-2
GSN	NM_001127663.2		c.99+766delT	intron	N/A	NP_001121135.2	A0A0A0MT01
GSN	NM_001353076.2		c.-48+1754delT	intron	N/A	NP_001340005.1	A0A8V8TND7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSN	ENST00000432226.7	TSL:5 MANE Select	c.-10+1754delT	intron	N/A	ENSP00000404226.2	P06396-2
GSN	ENST00000972594.1		c.-86delT	5_prime_UTR	Exon 2 of 18	ENSP00000642653.1
GSN	ENST00000900575.1		c.-10+1754delT	intron	N/A	ENSP00000570634.1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

50450

AN:

135838

Hom.:

10874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0992

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.609

Gnomad SAS

AF:

0.585

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.466

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.385

AC:

1810

AN:

4696

Hom.:

113

Cov.:

AF XY:

0.388

AC XY:

867

AN XY:

2234

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.387

AC:

1784

AN:

4608

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.340

AC:

AN:

Other (OTH)

AF:

0.267

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.371

AC:

50437

AN:

135840

Hom.:

10874

Cov.:

AF XY:

0.379

AC XY:

24691

AN XY:

65192

show subpopulations

African (AFR)

AF:

0.0991

AC:

3695

AN:

37286

American (AMR)

AF:

0.440

AC:

5990

AN:

13614

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1461

AN:

3290

East Asian (EAS)

AF:

0.610

AC:

2852

AN:

4678

South Asian (SAS)

AF:

0.586

AC:

2420

AN:

4132

European-Finnish (FIN)

AF:

0.536

AC:

3801

AN:

7096

Middle Eastern (MID)

AF:

0.463

AC:

125

AN:

270

European-Non Finnish (NFE)

AF:

0.459

AC:

28818

AN:

62788

Other (OTH)

AF:

0.426

AC:

788

AN:

1848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1149

2299

3448

4598

5747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.122

Hom.:

340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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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