rs2251411

Positions:

• chr1-51925920-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB3B	NM_002867.4	c.473-5806A>G		intron_variant		ENST00000371655.4	NP_002858.2
RAB3B	XM_017001958.2	c.473-5806A>G		intron_variant			XP_016857447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB3B	ENST00000371655.4	c.473-5806A>G		intron_variant		1	NM_002867.4	ENSP00000360718	P1

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

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.815

Alfa AF: 0.744 Hom.: 5319

Bravo AF: 0.809

Asia WGS AF: 0.902 AC: 3138 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	5.5
DANN	Benign	0.79

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: rs2251411; hg19: chr1-52391592; COSMIC: COSV65433800;