rs9409230

Variant names:

• chr9-121205482-A-T
• rs9409230
• ENST00000720058.1:n.420A>T

Variant summary

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

The ENST00000720058.1(ENSG00000293945):​n.420A>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 0.0389 in 152,276 control chromosomes in the GnomAD database, including 134 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 0.039 (134 hom., cov: 32)
• Consequence: ENSG00000293945 ENST00000720058.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759
• Publications: 5 publications found

Genes affected

ENSG00000293945 (HGNC:):

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSN	NM_001353053.1	c.-976-2318A>T		intron_variant	Intron 1 of 25		NP_001339982.1
GSN	NM_001353054.1	c.-905-2318A>T		intron_variant	Intron 1 of 25		NP_001339983.1
GSN	XM_047423267.1	c.-895-2318A>T		intron_variant	Intron 1 of 25		XP_047279223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293945	ENST00000720058.1	n.420A>T		non_coding_transcript_exon_variant	Exon 2 of 2
RAB14	ENST00000451303.1	c.-7-12063T>A		intron_variant	Intron 2 of 8	3		ENSP00000400107.1
ENSG00000293945	ENST00000720057.1	n.275-111A>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5916 AN: 152158 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0374

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

GnomAD4 genome AF: 0.0389 AC: 5918 AN: 152276 Hom.: 134 Cov.: 32 AF XY: 0.0367 AC XY: 2730 AN XY: 74466

African (AFR) AF: 0.0232 AC: 964 AN: 41568

American (AMR) AF: 0.0254 AC: 389 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3470

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5184

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4824

European-Finnish (FIN) AF: 0.0504 AC: 535 AN: 10614

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3744 AN: 68008

Other (OTH) AF: 0.0384 AC: 81 AN: 2108

Alfa AF: 0.0456 Hom.: 19

Bravo AF: 0.0376

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.84
PhyloP100		0.76

Splicing

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

Other links and lift over

dbSNP: rs9409230; hg19: chr9-123967760;