Genetic Variant ENST00000485767.1:n.2004G>T (chr9-121310374-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000485767.1(GSN):n.2004G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 409,426 control chromosomes in the GnomAD database, including 29,444 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 0.41 ( 14342 hom., cov: 32)

Exomes 𝑓: 0.33 ( 15102 hom. )

Consequence

GSN
ENST00000485767.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.197

Publications

20 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_198252.3 link	c.352-310G>T		intron_variant	Intron 4 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.352-310G>T		intron_variant	Intron 4 of 17	5	NM_198252.3	ENSP00000404226.2		P06396-2Q5T0I0

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62161

AN:

151858

Hom.:

14330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.328

AC:

84356

AN:

257450

Hom.:

15102

Cov.:

AF XY:

0.317

AC XY:

43820

AN XY:

138094

show subpopulations

African (AFR)

AF:

0.614

AC:

4631

AN:

7548

American (AMR)

AF:

0.247

AC:

2917

AN:

11796

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

2492

AN:

7226

East Asian (EAS)

AF:

0.108

AC:

1483

AN:

13718

South Asian (SAS)

AF:

0.225

AC:

8886

AN:

39578

European-Finnish (FIN)

AF:

0.332

AC:

4052

AN:

12198

Middle Eastern (MID)

AF:

0.310

AC:

314

AN:

1012

European-Non Finnish (NFE)

AF:

0.364

AC:

54749

AN:

150308

Other (OTH)

AF:

0.344

AC:

4832

AN:

14066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

2596

5193

7789

10386

12982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.409

AC:

62207

AN:

151976

Hom.:

14342

Cov.:

AF XY:

0.400

AC XY:

29739

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.612

AC:

25335

AN:

41406

American (AMR)

AF:

0.274

AC:

4184

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1092

AN:

3470

East Asian (EAS)

AF:

0.111

AC:

573

AN:

5180

South Asian (SAS)

AF:

0.221

AC:

1068

AN:

4824

European-Finnish (FIN)

AF:

0.332

AC:

3508

AN:

10562

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.373

AC:

25318

AN:

67948

Other (OTH)

AF:

0.363

AC:

765

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1717

3434

5152

6869

8586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.374

Hom.:

23395

Bravo

AF:

0.411

Asia WGS

AF:

0.219

AC:

760

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.0

(source)

DANN

Benign

0.48

PhyloP100

0.20

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