rs9408928

chr9-121189639-T-C

Variant summary

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

The NM_016322.4(RAB14):c.284+915A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,180 control chromosomes in the GnomAD database, including 169 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 0.043 (169 hom., cov: 32)
• Consequence: RAB14 NM_016322.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB14	NM_016322.4	c.284+915A>G		intron_variant		ENST00000373840.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB14	ENST00000373840.9	c.284+915A>G		intron_variant		1	NM_016322.4	P1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6513 AN: 152062 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0428 AC: 6515 AN: 152180 Hom.: 169 Cov.: 32 AF XY: 0.0408 AC XY: 3035 AN XY: 74400

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0644

Gnomad4 NFE AF: 0.0609

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0547 Hom.: 318

Bravo AF: 0.0405

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.0
Dann	Benign	0.87

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: rs9408928; hg19: chr9-123951917;