chr17-354346-C-G

Variant names:

• chr17-354346-C-G
• rs9915104
• ENST00000573780.5:c.-36-26767G>C

Variant summary

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

The ENST00000573780.5(RPH3AL):​c.-36-26767G>C variant causes a intron 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 ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 1 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000573780.5	c.-36-26767G>C		intron_variant	Intron 1 of 4	4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-212-20412G>C		intron_variant	Intron 1 of 4	4		ENSP00000460171.1
RPH3AL-AS2	ENST00000572499.1	n.225+1484C>G		intron_variant	Intron 1 of 1	3

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

African (AFR) AF: 0.208 AC: 8556 AN: 41154

American (AMR) AF: 0.414 AC: 6305 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3470

East Asian (EAS) AF: 0.108 AC: 553 AN: 5126

South Asian (SAS) AF: 0.447 AC: 2136 AN: 4780

European-Finnish (FIN) AF: 0.375 AC: 3909 AN: 10414

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30191 AN: 67796

Other (OTH) AF: 0.393 AC: 823 AN: 2096

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
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs9915104; hg19: chr17-204137;