9-121286020-G-A

Position:

• chr9-121286020-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198252.3(GSN):​c.-10+4458G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,054,198 control chromosomes in the GnomAD database, including 20,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3911 hom., cov: 33)
  • Exomes 𝑓: 0.18 (16394 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-121286020-G-A is Benign according to our data. Variant chr9-121286020-G-A is described in ClinVar as [Benign]. Clinvar id is 1279715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSN	NM_198252.3	c.-10+4458G>A		intron_variant		ENST00000432226.7	NP_937895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7	c.-10+4458G>A		intron_variant		5	NM_198252.3	ENSP00000404226	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32560 AN: 152090 Hom.: 3908 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0537

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.184 AC: 165661 AN: 901990 Hom.: 16394 AF XY: 0.181 AC XY: 83994 AN XY: 463504

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.0584

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.214 AC: 32584 AN: 152208 Hom.: 3911 Cov.: 33 AF XY: 0.210 AC XY: 15605 AN XY: 74418

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.170

Alfa AF: 0.210 Hom.: 1060

Bravo AF: 0.212

Asia WGS AF: 0.124 AC: 431 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.79
CADD	Benign	2.2
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs12683459; hg19: chr9-124048298;