9-121207556-C-T

Variant names:

• chr9-121207556-C-T
• rs7030849
• NM_001353053.1:c.-976-244C>T

Variant summary

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

The NM_001353053.1(GSN):​c.-976-244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,086 control chromosomes in the GnomAD database, including 21,894 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 0.51 (21894 hom., cov: 32)
• Consequence: GSN NM_001353053.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• 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]

RAB14 (HGNC:16524): (RAB14, member RAS oncogene family) RAB14 belongs to the large RAB family of low molecular mass GTPases that are involved in intracellular membrane trafficking. These proteins act as molecular switches that flip between an inactive GDP-bound state and an active GTP-bound state in which they recruit downstream effector proteins onto membranes (Junutula et al., 2004 [PubMed 15004230]).[supplied by OMIM, Mar 2009]

RAB14 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_001353053.1	c.-976-244C>T		intron_variant	Intron 1 of 25		NP_001339982.1
GSN	NM_001353054.1	c.-905-244C>T		intron_variant	Intron 1 of 25		NP_001339983.1
GSN	XM_047423267.1	c.-895-244C>T		intron_variant	Intron 1 of 25		XP_047279223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB14	ENST00000451303.1	c.-7-14137G>A		intron_variant	Intron 2 of 8	3		ENSP00000400107.1
GSN	ENST00000373823.7	c.-1149C>T		upstream_gene_variant		5		ENSP00000362929.2
GSN	ENST00000434663.5	n.-238C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77872 AN: 151968 Hom.: 21879 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.560

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.512 AC: 77923 AN: 152086 Hom.: 21894 Cov.: 32 AF XY: 0.522 AC XY: 38782 AN XY: 74326

African (AFR) AF: 0.273 AC: 11345 AN: 41498

American (AMR) AF: 0.662 AC: 10119 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2148 AN: 3468

East Asian (EAS) AF: 0.741 AC: 3834 AN: 5172

South Asian (SAS) AF: 0.804 AC: 3874 AN: 4820

European-Finnish (FIN) AF: 0.567 AC: 5989 AN: 10560

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38598 AN: 67968

Other (OTH) AF: 0.562 AC: 1185 AN: 2110

Alfa AF: 0.550 Hom.: 4966

Bravo AF: 0.509

Asia WGS AF: 0.709 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.48
PhyloP100		-0.050
PromoterAI		0.010	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7030849; hg19: chr9-123969834; COSMIC: COSV65743803;