rs2271882

Positions:

• chr19-18198555-A-G
• chr19-18198555-A-T

Variant summary

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

The NM_002866.5(RAB3A):​c.472+170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,010 control chromosomes in the GnomAD database, including 31,210 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 0.63 (31210 hom., cov: 31)
• Consequence: RAB3A NM_002866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

Genes affected

RAB3A (HGNC:9777): (RAB3A, member RAS oncogene family) Enables GTPase activity and myosin V binding activity. Involved in several processes, including acrosomal vesicle exocytosis; lysosome localization; and plasma membrane repair. Located in perinuclear region of cytoplasm. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3A	NM_002866.5	c.472+170T>C		intron_variant		ENST00000222256.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3A	ENST00000222256.9	c.472+170T>C		intron_variant		1	NM_002866.5	P1
RAB3A	ENST00000464076.3	c.187+170T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95516 AN: 151892 Hom.: 31175 Cov.: 31

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.629 AC: 95617 AN: 152010 Hom.: 31210 Cov.: 31 AF XY: 0.626 AC XY: 46555 AN XY: 74312

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.644

Alfa AF: 0.680 Hom.: 73459

Bravo AF: 0.614

Asia WGS AF: 0.318 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs2271882; hg19: chr19-18309365; COSMIC: COSV55852883; COSMIC: COSV55852883;