9-121280666-C-T

Variant names:

• chr9-121280666-C-T
• rs306781
• NM_198252.3:c.-102-804C>T

Variant summary

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

The NM_198252.3(GSN):​c.-102-804C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 152,332 control chromosomes in the GnomAD database, including 73,979 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 0.99 (73979 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• Publications: 4 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]

ENSG00000239593 (HGNC:):

GSN-AS1 (HGNC:23372): (GSN antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	NM_198252.3	MANE Select	c.-102-804C>T		intron	N/A	NP_937895.1	P06396-2
	GSN	NM_001127663.2		c.-106-804C>T		intron	N/A	NP_001121135.2	A0A0A0MT01
	GSN	NM_001353076.2		c.-140-804C>T		intron	N/A	NP_001340005.1	A0A8V8TND7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSN	ENST00000432226.7	TSL:5 MANE Select	c.-102-804C>T		intron	N/A	ENSP00000404226.2	P06396-2
	GSN	ENST00000900575.1		c.-102-804C>T		intron	N/A	ENSP00000570634.1
	GSN	ENST00000449733.7	TSL:2	c.-106-804C>T		intron	N/A	ENSP00000409358.2	A0A0A0MT01

Frequencies

GnomAD3 genomes AF: 0.985 AC: 149995 AN: 152212 Hom.: 73917 Cov.: 32

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.983

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.985 AC: 150116 AN: 152330 Hom.: 73979 Cov.: 32 AF XY: 0.986 AC XY: 73475 AN XY: 74494

African (AFR) AF: 0.994 AC: 41297 AN: 41566

American (AMR) AF: 0.981 AC: 15011 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3360 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.994 AC: 4789 AN: 4816

European-Finnish (FIN) AF: 0.996 AC: 10588 AN: 10626

Middle Eastern (MID) AF: 0.983 AC: 287 AN: 292

European-Non Finnish (NFE) AF: 0.979 AC: 66606 AN: 68042

Other (OTH) AF: 0.983 AC: 2079 AN: 2114

Alfa AF: 0.981 Hom.: 133262

Bravo AF: 0.985

Asia WGS AF: 0.995 AC: 3460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.056
DANN	Benign	0.55
PhyloP100		-0.86
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: rs306781; hg19: chr9-124042944;