rs74647838

Variant names:

• chr12-112695096-G-A
• rs74647838
• NM_001347952.2:c.-139-97047G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-112695096-G-A
• chr12-112695096-G-T

Variant summary

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

The NM_001347952.2(RPH3A):​c.-139-97047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 170,458 control chromosomes in the GnomAD database, including 160 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 0.025 (160 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: RPH3A NM_001347952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 7 publications found

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]

MIR1302-1 (HGNC:35293): (microRNA 1302-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347952.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	NM_001347952.2		c.-139-97047G>A		intron	N/A	NP_001334881.1	Q9Y2J0-1
	MIR1302-1	NR_031631.1		n.81C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3A	ENST00000543106.6	TSL:2	c.-139-97047G>A		intron	N/A	ENSP00000440384.2	Q9Y2J0-1
	RPH3A	ENST00000942157.1		c.-140+82163G>A		intron	N/A	ENSP00000612216.1
	RPH3A	ENST00000942158.1		c.-19+43269G>A		intron	N/A	ENSP00000612217.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3765 AN: 152148 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00664 AC: 156 AN: 23496 AF XY: 0.00534

Gnomad AFR exome AF: 0.0793

Gnomad AMR exome AF: 0.0150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000808

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000220 AC: 4 AN: 18192 Hom.: 0 Cov.: 0 AF XY: 0.000230 AC XY: 2 AN XY: 8700

African (AFR) AF: 0.0256 AC: 2 AN: 78

American (AMR) AF: 0.00 AC: 0 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 94

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15812

Middle Eastern (MID) AF: 0.00122 AC: 2 AN: 1634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 264

Other (OTH) AF: 0.00 AC: 0 AN: 290

GnomAD4 genome AF: 0.0247 AC: 3768 AN: 152266 Hom.: 160 Cov.: 33 AF XY: 0.0238 AC XY: 1773 AN XY: 74452

African (AFR) AF: 0.0854 AC: 3547 AN: 41530

American (AMR) AF: 0.0104 AC: 159 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68018

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.0147 Hom.: 21

Bravo AF: 0.0285

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.68
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs74647838; hg19: chr12-113132901;