17-354346-C-G

Position:

• chr17-354346-C-G

Variant summary

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

The ENST00000572499.1(RPH3AL-AS2):​n.225+1484C>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,254 control chromosomes in the GnomAD database, including 10,754 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 0.36 (10754 hom., cov: 30)
• Consequence: RPH3AL-AS2 ENST00000572499.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701

Genes affected

RPH3AL-AS2 (HGNC:56089): (RPH3AL antisense RNA 2)

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3AL-AS2	ENST00000572499.1	n.225+1484C>G		intron_variant, non_coding_transcript_variant		3
RPH3AL	ENST00000573780.5	c.-36-26767G>C		intron_variant		4		ENSP00000459992
RPH3AL	ENST00000575130.5	c.-212-20412G>C		intron_variant		4		ENSP00000460171

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54423 AN: 151134 Hom.: 10742 Cov.: 30

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.360 AC: 54445 AN: 151254 Hom.: 10754 Cov.: 30 AF XY: 0.358 AC XY: 26472 AN XY: 73874

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.393

Alfa AF: 0.397 Hom.: 1563

Bravo AF: 0.354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.88
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9915104; hg19: chr17-204137;