rs306784

Variant names:

• chr9-121310374-G-C
• rs306784
• ENST00000485767.1:n.2004G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-121310374-G-C
• chr9-121310374-G-T

Variant summary

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

The ENST00000485767.1(GSN):​n.2004G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000775 in 258,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: GSN ENST00000485767.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 0 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=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_198252.3	c.352-310G>C		intron_variant	Intron 4 of 17	ENST00000432226.7	NP_937895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSN	ENST00000432226.7	c.352-310G>C		intron_variant	Intron 4 of 17	5	NM_198252.3	ENSP00000404226.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000775 AC: 2 AN: 258028 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 138368

African (AFR) AF: 0.00 AC: 0 AN: 7562

American (AMR) AF: 0.00 AC: 0 AN: 11818

Ashkenazi Jewish (ASJ) AF: 0.000138 AC: 1 AN: 7242

East Asian (EAS) AF: 0.00 AC: 0 AN: 13724

South Asian (SAS) AF: 0.00 AC: 0 AN: 39638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1014

European-Non Finnish (NFE) AF: 0.00000664 AC: 1 AN: 150684

Other (OTH) AF: 0.00 AC: 0 AN: 14106

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.35
PhyloP100		0.20

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: rs306784; hg19: chr9-124072652;