9-121282717-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198252.3(GSN):c.-10+1155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 412,926 control chromosomes in the GnomAD database, including 44,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (13577 hom., cov: 32)
  • Exomes 𝑓: 0.48 (30764 hom.)
• Consequence: GSN NM_198252.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-121282717-C-T is Benign according to our data. Variant chr9-121282717-C-T is described in ClinVar as [Benign]. Clinvar id is 1244182.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSN	NM_198252.3	c.-10+1155C>T		intron_variant		ENST00000432226.7
GSN-AS1	NR_103560.1	n.2814G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSN	ENST00000432226.7	c.-10+1155C>T		intron_variant		5	NM_198252.3	P1
GSN-AS1	ENST00000414544.1	n.2814G>A		non_coding_transcript_exon_variant	1/1
	ENST00000437135.1	n.14G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57538 AN: 152000 Hom.: 13565 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.478 AC: 124759 AN: 260810 Hom.: 30764 Cov.: 3 AF XY: 0.480 AC XY: 63168 AN XY: 131730

Gnomad4 AFR exome AF: 0.0992

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.450

GnomAD4 genome AF: 0.378 AC: 57556 AN: 152116 Hom.: 13577 Cov.: 32 AF XY: 0.388 AC XY: 28885 AN XY: 74364

Gnomad4 AFR AF: 0.0893

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.436

Alfa AF: 0.437 Hom.: 18733

Bravo AF: 0.357

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.71
Dann	Benign	0.44

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: rs3810942; hg19: chr9-124044995; COSMIC: COSV57994512; COSMIC: COSV57994512;