Genetic Variant NM_198252.3:c.-10+7560A>G (chr9-121289122-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198252.3(GSN):c.-10+7560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 151,962 control chromosomes in the GnomAD database, including 37,500 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 0.70 ( 37500 hom., cov: 31)

Consequence

GSN
NM_198252.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.883

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_198252.3 link	c.-10+7560A>G		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+7560A>G		intron_variant	Intron 2 of 17	5	NM_198252.3	ENSP00000404226.2		P06396-2Q5T0I0

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106274

AN:

151846

Hom.:

37461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.751

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.817

Gnomad SAS

AF:

0.813

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.683

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.700

AC:

106363

AN:

151962

Hom.:

37500

Cov.:

AF XY:

0.708

AC XY:

52553

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.689

Gnomad4 AMR

AF:

0.752

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.817

Gnomad4 SAS

AF:

0.812

Gnomad4 FIN

AF:

0.770

Gnomad4 NFE

AF:

0.675

Gnomad4 OTH

AF:

0.685

Alfa

AF:

0.676

Hom.:

45981

Bravo

AF:

0.696

Asia WGS

AF:

0.777

AC:

2702

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.086

DANN

Benign

0.60

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over