9-121289122-A-G

Variant names:

• chr9-121289122-A-G
• rs1078305
• NM_198252.3:c.-10+7560A>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198252.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	NM_198252.3	MANE Select	c.-10+7560A>G		intron	N/A	NP_937895.1
	GSN	NM_001127663.2		c.99+6572A>G		intron	N/A	NP_001121135.2
	GSN	NM_001353076.2		c.-48+7560A>G		intron	N/A	NP_001340005.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	ENST00000432226.7	TSL:5 MANE Select	c.-10+7560A>G		intron	N/A	ENSP00000404226.2
	GSN	ENST00000449733.7	TSL:2	c.99+6572A>G		intron	N/A	ENSP00000409358.2
	GSN	ENST00000699558.1		c.-48+7560A>G		intron	N/A	ENSP00000514432.1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106274 AN: 151846 Hom.: 37461 Cov.: 31

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.: 31 AF XY: 0.708 AC XY: 52553 AN XY: 74258

African (AFR) AF: 0.689 AC: 28541 AN: 41450

American (AMR) AF: 0.752 AC: 11493 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3472

East Asian (EAS) AF: 0.817 AC: 4226 AN: 5174

South Asian (SAS) AF: 0.812 AC: 3905 AN: 4808

European-Finnish (FIN) AF: 0.770 AC: 8114 AN: 10536

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45830 AN: 67916

Other (OTH) AF: 0.685 AC: 1446 AN: 2110

Alfa AF: 0.678 Hom.: 58561

Bravo AF: 0.696

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.086
DANN	Benign	0.60
PhyloP100		-0.88
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: rs1078305; hg19: chr9-124051400; COSMIC: COSV57995433; COSMIC: COSV57995433;