chr12-112721033-G-A

Position:

• chr12-112721033-G-A

Variant summary

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

The NM_001347952.2(RPH3A):​c.-139-71110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,010 control chromosomes in the GnomAD database, including 1,813 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 0.15 (1813 hom., cov: 32)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPH3A	NM_001347952.2	c.-139-71110G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3A	ENST00000543106.6	c.-139-71110G>A		intron_variant		2		P3
RPH3A	ENST00000546426.5	c.-140+69206G>A		intron_variant		4
RPH3A	ENST00000546703.5	c.-139-71110G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22842 AN: 151892 Hom.: 1791 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.151 AC: 22921 AN: 152010 Hom.: 1813 Cov.: 32 AF XY: 0.149 AC XY: 11100 AN XY: 74304

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0952

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0907

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0869 Hom.: 186

Bravo AF: 0.153

Asia WGS AF: 0.157 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.4
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7312122; hg19: chr12-113158838;