Variant 9-121282470-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001127663.2(GSN):c.19C>T(p.Arg7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,267,542 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00038 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00035 ( 2 hom. )

Consequence

GSN
NM_001127663.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0570

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:):

GSN-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040370256).

BP6

Variant 9-121282470-C-T is Benign according to our data. Variant chr9-121282470-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3058775.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000381 (58/152316) while in subpopulation SAS AF= 0.000622 (3/4826). AF 95% confidence interval is 0.000292. There are 1 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 58 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSN	NM_198252.3 linkuse as main transcript	c.-10+908C>T		intron_variant		ENST00000432226.7	NP_937895.1	P06396-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7 linkuse as main transcript	c.-10+908C>T		intron_variant		5	NM_198252.3	ENSP00000404226.2		P06396-2Q5T0I0

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000352

AC:

393

AN:

1115226

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

184

AN XY:

527884

show subpopulations

Gnomad4 AFR exome

AF:

0.000128

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000815

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00213

Gnomad4 NFE exome

AF:

0.000272

Gnomad4 OTH exome

AF:

0.000493

GnomAD4 genome

AF:

0.000381

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000454

Hom.:

Bravo

AF:

0.000204

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GSN-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 09, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.9

DANN

Benign

0.70

DEOGEN2

Benign

0.0061

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.48

MetaRNN

Benign

0.040

Vest4

0.041

MVP

0.67

GERP RS

0.96

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