rs10985196

Positions:

• chr9-121270766-C-A
• chr9-121270766-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198252.3(GSN):​c.-103+2547C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,030 control chromosomes in the GnomAD database, including 7,000 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 0.28 (7000 hom., cov: 32)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSN	NM_198252.3	c.-103+2547C>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.-103+2547C>A		intron_variant		5	NM_198252.3	ENSP00000404226	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42535 AN: 151910 Hom.: 6985 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.280 AC: 42583 AN: 152030 Hom.: 7000 Cov.: 32 AF XY: 0.279 AC XY: 20701 AN XY: 74298

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.222

Alfa AF: 0.201 Hom.: 3181

Bravo AF: 0.293

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.71

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: rs10985196; hg19: chr9-124033044;