rs4617924

Positions:

• chr17-264878-C-A

Variant summary

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

The NM_006987.4(RPH3AL):​c.438+16890G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,034 control chromosomes in the GnomAD database, including 19,590 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 0.51 (19590 hom., cov: 33)
• Consequence: RPH3AL NM_006987.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPH3AL	NM_006987.4	c.438+16890G>T		intron_variant		ENST00000331302.12	NP_008918.1
RPH3AL	NM_001190411.2	c.438+16890G>T		intron_variant			NP_001177340.1
RPH3AL	NM_001190412.2	c.352-17593G>T		intron_variant			NP_001177341.1
RPH3AL	NM_001190413.2	c.352-17593G>T		intron_variant			NP_001177342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000331302.12	c.438+16890G>T		intron_variant		2	NM_006987.4	ENSP00000328977	P1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76891 AN: 151914 Hom.: 19561 Cov.: 33

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.506 AC: 76963 AN: 152034 Hom.: 19590 Cov.: 33 AF XY: 0.509 AC XY: 37855 AN XY: 74324

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.533

Alfa AF: 0.498 Hom.: 33975

Bravo AF: 0.506

Asia WGS AF: 0.617 AC: 2144 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	8.5
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4617924; hg19: chr17-114669; COSMIC: COSV58747190;