NM_001353053.1:c.-460+16513G>A

Variant names:

• chr9-121247816-G-A
• rs4837820
• NM_001353053.1:c.-460+16513G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353053.1(GSN):​c.-460+16513G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,208 control chromosomes in the GnomAD database, including 13,503 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 0.38 (13503 hom., cov: 29)
• Consequence: GSN NM_001353053.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• Finnish type amyloidosis

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_001353053.1	c.-460+16513G>A		intron_variant	Intron 6 of 25		NP_001339982.1
GSN	NM_001353054.1	c.-388-460G>A		intron_variant	Intron 6 of 25		NP_001339983.1
GSN	XM_047423267.1	c.-379+16513G>A		intron_variant	Intron 6 of 25		XP_047279223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000373823.7	c.-388-460G>A		intron_variant	Intron 5 of 24	5		ENSP00000362929.2
GSN	ENST00000434663.5	n.523+16513G>A		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57171 AN: 151090 Hom.: 13489 Cov.: 29

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.378 AC: 57189 AN: 151208 Hom.: 13503 Cov.: 29 AF XY: 0.388 AC XY: 28577 AN XY: 73724

African (AFR) AF: 0.0888 AC: 3675 AN: 41370

American (AMR) AF: 0.446 AC: 6763 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1632 AN: 3456

East Asian (EAS) AF: 0.621 AC: 3144 AN: 5066

South Asian (SAS) AF: 0.603 AC: 2878 AN: 4772

European-Finnish (FIN) AF: 0.559 AC: 5760 AN: 10308

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31731 AN: 67778

Other (OTH) AF: 0.436 AC: 917 AN: 2104

Alfa AF: 0.453 Hom.: 8715

Bravo AF: 0.357

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.4
DANN	Benign	0.64
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4837820; hg19: chr9-124010094; COSMIC: COSV65743847;