9-121285850-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198252.3(GSN):c.-10+4288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 152,300 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.015 (33 hom., cov: 33)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.442

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-121285850-C-T is Benign according to our data. Variant chr9-121285850-C-T is described in ClinVar as [Benign]. Clinvar id is 1257589.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0151 (2304/152300) while in subpopulation NFE AF= 0.0194 (1318/68028). AF 95% confidence interval is 0.0185. There are 33 homozygotes in gnomad4. There are 1247 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2306 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.-10+4288C>T		intron_variant		ENST00000432226.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.-10+4288C>T		intron_variant		5	NM_198252.3	P1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2306 AN: 152182 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0138

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

GnomAD4 genome AF: 0.0151 AC: 2304 AN: 152300 Hom.: 33 Cov.: 33 AF XY: 0.0167 AC XY: 1247 AN XY: 74466

Gnomad4 AFR AF: 0.00245

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0625

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0175 Hom.: 3

Bravo AF: 0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.2
Dann	Benign	0.27

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: rs117965336; hg19: chr9-124048128;