rs4247113

Variant names:

• chr17-379187-C-T
• rs4247113
• ENST00000573780.5:c.-37+7010G>A

Variant summary

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

The ENST00000573780.5(RPH3AL):​c.-37+7010G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,098 control chromosomes in the GnomAD database, including 3,924 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 0.18 (3924 hom., cov: 31)
• Consequence: RPH3AL ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

Genes affected

RPH3AL (HGNC:10296): (rabphilin 3A like (without C2 domains)) The protein encoded by this gene plays a direct regulatory role in calcium-ion-dependent exocytosis in both endocrine and exocrine cells and plays a key role in insulin secretion by pancreatic cells. This gene is likely a tumor suppressor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000573780.5	c.-37+7010G>A		intron_variant	Intron 1 of 4	4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-213+7010G>A		intron_variant	Intron 1 of 4	4		ENSP00000460171.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27010 AN: 151980 Hom.: 3920 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0950

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.178 AC: 27033 AN: 152098 Hom.: 3924 Cov.: 31 AF XY: 0.180 AC XY: 13373 AN XY: 74346

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0950

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.170

Alfa AF: 0.0895 Hom.: 1169

Bravo AF: 0.197

Asia WGS AF: 0.242 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4247113; hg19: chr17-228978;