rs7046030

chr9-121284959-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198252.3(GSN):c.-10+3397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 167,134 control chromosomes in the GnomAD database, including 4,767 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 0.23 (4525 hom., cov: 32)
  • Exomes 𝑓: 0.18 (242 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.-10+3397T>C		intron_variant		ENST00000432226.7
GSN-AS1	NR_103560.1	n.572A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.-10+3397T>C		intron_variant		5	NM_198252.3	P1
GSN-AS1	ENST00000414544.1	n.572A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34304 AN: 151854 Hom.: 4520 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.178 AC: 2691 AN: 15160 Hom.: 242 Cov.: 0 AF XY: 0.174 AC XY: 1259 AN XY: 7242

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.226 AC: 34333 AN: 151974 Hom.: 4525 Cov.: 32 AF XY: 0.221 AC XY: 16421 AN XY: 74286

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0534

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.173

Alfa AF: 0.195 Hom.: 5361

Bravo AF: 0.226

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs7046030; hg19: chr9-124047237; COSMIC: COSV57994518; COSMIC: COSV57994518;