9-121189407-C-T

Variant names:

• chr9-121189407-C-T
• rs942152
• NM_016322.4:c.284+1147G>A

Variant summary

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

The NM_016322.4(RAB14):​c.284+1147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,888 control chromosomes in the GnomAD database, including 25,804 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 0.57 (25804 hom., cov: 32)
• Consequence: RAB14 NM_016322.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 20 publications found

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]

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB14	NM_016322.4	c.284+1147G>A		intron_variant	Intron 4 of 7	ENST00000373840.9	NP_057406.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB14	ENST00000373840.9	c.284+1147G>A		intron_variant	Intron 4 of 7	1	NM_016322.4	ENSP00000362946.4

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87115 AN: 151770 Hom.: 25770 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.574 AC: 87200 AN: 151888 Hom.: 25804 Cov.: 32 AF XY: 0.581 AC XY: 43099 AN XY: 74228

African (AFR) AF: 0.490 AC: 20288 AN: 41404

American (AMR) AF: 0.687 AC: 10482 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2256 AN: 3472

East Asian (EAS) AF: 0.924 AC: 4789 AN: 5184

South Asian (SAS) AF: 0.808 AC: 3898 AN: 4824

European-Finnish (FIN) AF: 0.541 AC: 5702 AN: 10544

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37654 AN: 67900

Other (OTH) AF: 0.622 AC: 1312 AN: 2108

Alfa AF: 0.577 Hom.: 53122

Bravo AF: 0.582

Asia WGS AF: 0.817 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.31
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs942152; hg19: chr9-123951685; COSMIC: COSV65788191;