rs306783

Variant names:

• chr9-121310319-C-T
• rs306783
• ENST00000485767.1:n.1949C>T

Variant summary

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

The ENST00000485767.1(GSN):​n.1949C>T 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 0.4 in 334,032 control chromosomes in the GnomAD database, including 28,035 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 0.41 (13422 hom., cov: 31)
  • Exomes 𝑓: 0.39 (14613 hom.)
• Consequence: GSN ENST00000485767.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_198252.3	c.352-365C>T		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.352-365C>T		intron_variant	Intron 4 of 17	5	NM_198252.3	ENSP00000404226.2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62779 AN: 151816 Hom.: 13426 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.389 AC: 70838 AN: 182098 Hom.: 14613 Cov.: 0 AF XY: 0.383 AC XY: 37693 AN XY: 98538

African (AFR) AF: 0.478 AC: 2500 AN: 5226

American (AMR) AF: 0.313 AC: 2396 AN: 7646

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1579 AN: 4458

East Asian (EAS) AF: 0.104 AC: 831 AN: 7980

South Asian (SAS) AF: 0.343 AC: 11727 AN: 34234

European-Finnish (FIN) AF: 0.388 AC: 3278 AN: 8450

Middle Eastern (MID) AF: 0.370 AC: 241 AN: 652

European-Non Finnish (NFE) AF: 0.428 AC: 44703 AN: 104404

Other (OTH) AF: 0.396 AC: 3583 AN: 9048

GnomAD4 genome AF: 0.413 AC: 62802 AN: 151934 Hom.: 13422 Cov.: 31 AF XY: 0.406 AC XY: 30160 AN XY: 74254

African (AFR) AF: 0.475 AC: 19687 AN: 41410

American (AMR) AF: 0.331 AC: 5054 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1109 AN: 3470

East Asian (EAS) AF: 0.112 AC: 577 AN: 5164

South Asian (SAS) AF: 0.332 AC: 1603 AN: 4822

European-Finnish (FIN) AF: 0.386 AC: 4068 AN: 10528

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.434 AC: 29503 AN: 67950

Other (OTH) AF: 0.389 AC: 821 AN: 2108

Alfa AF: 0.423 Hom.: 7696

Bravo AF: 0.407

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.81
PhyloP100		0.45
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: rs306783; hg19: chr9-124072597;