chr17-379187-C-T

Position:

• chr17-379187-C-T

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]

(HGNC:):

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/exons	MANE	Protein	UniProt
		n.379187C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000573780.5	c.-37+7010G>A		intron_variant		4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-213+7010G>A		intron_variant		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;