rs11614063

Positions:

• chr12-112587857-G-A
• chr12-112587857-G-C
• chr12-112587857-G-T

Variant summary

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

The NM_001347952.2(RPH3A):​c.-140+12538G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,016 control chromosomes in the GnomAD database, including 5,318 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 0.23 (5318 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPH3A	NM_001347952.2	c.-140+12538G>A		intron_variant			NP_001334881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3A	ENST00000543106.6	c.-140+12538G>A		intron_variant		2		ENSP00000440384.2
RPH3A	ENST00000551593.5	c.-19+12538G>A		intron_variant		4		ENSP00000446780.1
RPH3A	ENST00000548197.5	c.-140+17313G>A		intron_variant		4		ENSP00000446570.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34250 AN: 151898 Hom.: 5299 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.226 AC: 34324 AN: 152016 Hom.: 5318 Cov.: 32 AF XY: 0.230 AC XY: 17121 AN XY: 74306

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0652

Gnomad4 EAS AF: 0.0830

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.203

Alfa AF: 0.141 Hom.: 2048

Bravo AF: 0.226

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11614063; hg19: chr12-113025661;