rs321663

Positions:

• chr18-8636002-T-C

Variant summary

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

The NM_001025300.3(RAB12):​c.805-251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,138 control chromosomes in the GnomAD database, including 7,164 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 0.25 (7164 hom., cov: 33)
• Consequence: RAB12 NM_001025300.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

Genes affected

RAB12 (HGNC:31332): (RAB12, member RAS oncogene family) Enables GDP binding activity. Predicted to be involved in several processes, including cellular response to insulin stimulus; endosome to lysosome transport; and secretion by cell. Predicted to act upstream of or within cellular response to interferon-gamma. Predicted to be located in lysosome; phagocytic vesicle; and recycling endosome membrane. Predicted to be active in Golgi apparatus; cytoplasmic vesicle; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB12	NM_001025300.3	c.805-251T>C		intron_variant		ENST00000649141.2
RAB12	XM_006722300.4	c.421-251T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB12	ENST00000649141.2	c.805-251T>C		intron_variant			NM_001025300.3	P1
	ENST00000580267.1	n.159+187A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38207 AN: 152020 Hom.: 7146 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0317

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.252 AC: 38283 AN: 152138 Hom.: 7164 Cov.: 33 AF XY: 0.246 AC XY: 18314 AN XY: 74394

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.217

Alfa AF: 0.167 Hom.: 3530

Bravo AF: 0.264

Asia WGS AF: 0.126 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.64

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: rs321663; hg19: chr18-8636000;