NM_002867.4:c.347+860C>T

Variant names:

• chr1-51936434-G-A
• rs3765687
• NM_002867.4:c.347+860C>T

Variant summary

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

The NM_002867.4(RAB3B):​c.347+860C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,998 control chromosomes in the GnomAD database, including 22,234 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 0.53 (22234 hom., cov: 32)
• Consequence: RAB3B NM_002867.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• 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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3B	NM_002867.4	c.347+860C>T		intron_variant	Intron 3 of 4	ENST00000371655.4	NP_002858.2
RAB3B	XM_017001958.2	c.347+860C>T		intron_variant	Intron 3 of 4		XP_016857447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3B	ENST00000371655.4	c.347+860C>T		intron_variant	Intron 3 of 4	1	NM_002867.4	ENSP00000360718.3

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79908 AN: 151880 Hom.: 22217 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.526 AC: 79945 AN: 151998 Hom.: 22234 Cov.: 32 AF XY: 0.528 AC XY: 39248 AN XY: 74284

African (AFR) AF: 0.341 AC: 14152 AN: 41442

American (AMR) AF: 0.620 AC: 9473 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2094 AN: 3466

East Asian (EAS) AF: 0.853 AC: 4423 AN: 5184

South Asian (SAS) AF: 0.519 AC: 2506 AN: 4824

European-Finnish (FIN) AF: 0.569 AC: 5998 AN: 10550

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39386 AN: 67942

Other (OTH) AF: 0.567 AC: 1197 AN: 2112

Alfa AF: 0.553 Hom.: 5724

Bravo AF: 0.524

Asia WGS AF: 0.667 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.9
DANN	Benign	0.87
PhyloP100		0.051
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3765687; hg19: chr1-52402106; COSMIC: COSV65433829;