rs1078305

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-121289122-A-C
• chr9-121289122-A-G
• chr9-121289122-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198252.3(GSN):​c.-10+7560A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>C		intron	N/A	NP_937895.1
	GSN	NM_001127663.2		c.99+6572A>C		intron	N/A	NP_001121135.2
	GSN	NM_001353076.2		c.-48+7560A>C		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>C		intron	N/A	ENSP00000404226.2
	GSN	ENST00000449733.7	TSL:2	c.99+6572A>C		intron	N/A	ENSP00000409358.2
	GSN	ENST00000699558.1		c.-48+7560A>C		intron	N/A	ENSP00000514432.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.076
DANN	Benign	0.63
PhyloP100		-0.88

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;