rs17824620

Positions:

• chr12-112663189-C-A

Variant summary

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

The NM_001347952.2(RPH3A):​c.-140+87870C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,648 control chromosomes in the GnomAD database, including 6,059 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 0.26 (6059 hom., cov: 30)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

Genes affected

RPH3A (HGNC:17056): (rabphilin 3A) The protein encoded by this gene is thought to be an effector for RAB3A, which is a small G protein that acts in the late stages of neurotransmitter exocytosis. The encoded protein may be involved in neurotransmitter release and synaptic vesicle traffic. [provided by RefSeq, Dec 2016]

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 (AMR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPH3A	NM_001347952.2	c.-140+87870C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3A	ENST00000543106.6	c.-140+87870C>A		intron_variant		2		P3
RPH3A	ENST00000546426.5	c.-140+11362C>A		intron_variant		4
RPH3A	ENST00000546703.5	c.-140+45347C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39603 AN: 151532 Hom.: 6054 Cov.: 30

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.261 AC: 39617 AN: 151648 Hom.: 6059 Cov.: 30 AF XY: 0.270 AC XY: 19994 AN XY: 74060

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.270

Alfa AF: 0.290 Hom.: 6502

Bravo AF: 0.242

Asia WGS AF: 0.281 AC: 976 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	4.3
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17824620; hg19: chr12-113100994;