Variant 9-121282717-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198252.3(GSN):c.-10+1155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 412,926 control chromosomes in the GnomAD database, including 44,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13577 hom., cov: 32)

Exomes 𝑓: 0.48 ( 30764 hom. )

Consequence

GSN
NM_198252.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.36

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-121282717-C-T is Benign according to our data. Variant chr9-121282717-C-T is described in ClinVar as [Benign]. Clinvar id is 1244182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSN	NM_198252.3 linkuse as main transcript	c.-10+1155C>T		intron_variant		ENST00000432226.7	NP_937895.1
GSN-AS1	NR_103560.1 linkuse as main transcript	n.2814G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7 linkuse as main transcript	c.-10+1155C>T	intron_variant		5	NM_198252.3	ENSP00000404226	P1	P06396-2
GSN-AS1	ENST00000414544.1 linkuse as main transcript	n.2814G>A	non_coding_transcript_exon_variant	1/1
	ENST00000437135.1 linkuse as main transcript	n.14G>A	non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57538

AN:

152000

Hom.:

13565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.433

GnomAD4 exome

AF:

0.478

AC:

124759

AN:

260810

Hom.:

30764

Cov.:

AF XY:

0.480

AC XY:

63168

AN XY:

131730

show subpopulations

Gnomad4 AFR exome

AF:

0.0992

Gnomad4 AMR exome

AF:

0.451

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.610

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.470

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.378

AC:

57556

AN:

152116

Hom.:

13577

Cov.:

AF XY:

0.388

AC XY:

28885

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0893

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.621

Gnomad4 SAS

AF:

0.603

Gnomad4 FIN

AF:

0.559

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.436

Alfa

AF:

0.437

Hom.:

18733

Bravo

AF:

0.357

Asia WGS

AF:

0.542

AC:

1884

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.71

DANN

Benign

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over