rs2251411

Variant names:

• chr1-51925920-T-C
• rs2251411
• NM_002867.4:c.473-5806A>G

Variant summary

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

The NM_002867.4(RAB3B):​c.473-5806A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,202 control chromosomes in the GnomAD database, including 48,145 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 0.79 (48145 hom., cov: 33)
• Consequence: RAB3B NM_002867.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483
• Publications: 1 publications found

Genes affected

RAB3B (HGNC:9778): (RAB3B, member RAS oncogene family) Enables GDP binding activity; GTPase activity; and myosin V binding activity. Involved in several processes, including positive regulation of dopamine uptake involved in synaptic transmission; regulation of synaptic vesicle cycle; and regulation of vesicle size. Located in perinuclear region of cytoplasm and vesicle. Is active in dopaminergic synapse. Is anchored component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002867.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3B	NM_002867.4	MANE Select	c.473-5806A>G		intron	N/A	NP_002858.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3B	ENST00000371655.4	TSL:1 MANE Select	c.473-5806A>G		intron	N/A	ENSP00000360718.3

Frequencies

GnomAD3 genomes AF: 0.789 AC: 120035 AN: 152084 Hom.: 48103 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.789 AC: 120134 AN: 152202 Hom.: 48145 Cov.: 33 AF XY: 0.789 AC XY: 58671 AN XY: 74394

African (AFR) AF: 0.898 AC: 37329 AN: 41548

American (AMR) AF: 0.839 AC: 12833 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2817 AN: 3468

East Asian (EAS) AF: 0.988 AC: 5119 AN: 5182

South Asian (SAS) AF: 0.789 AC: 3806 AN: 4822

European-Finnish (FIN) AF: 0.649 AC: 6852 AN: 10564

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48788 AN: 68002

Other (OTH) AF: 0.815 AC: 1721 AN: 2112

Alfa AF: 0.749 Hom.: 5623

Bravo AF: 0.809

Asia WGS AF: 0.902 AC: 3138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.79
PhyloP100		0.48
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: rs2251411; hg19: chr1-52391592; COSMIC: COSV65433800;