17-353740-G-T

Variant names:

• chr17-353740-G-T
• rs28687962
• ENST00000573780.5:c.-36-26161C>A

Variant summary

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

The ENST00000573780.5(RPH3AL):​c.-36-26161C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 123,946 control chromosomes in the GnomAD database, including 10,276 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 0.33 (10276 hom., cov: 31)
• Consequence: RPH3AL ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 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.-36-26161C>A		intron_variant	Intron 1 of 4	4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-212-19806C>A		intron_variant	Intron 1 of 4	4		ENSP00000460171.1
RPH3AL-AS2	ENST00000572499.1	n.225+878G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 40899 AN: 123826 Hom.: 10275 Cov.: 31

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.330 AC: 40930 AN: 123946 Hom.: 10276 Cov.: 31 AF XY: 0.338 AC XY: 20410 AN XY: 60468

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.293

Alfa AF: 0.243 Hom.: 873

Bravo AF: 0.356

Asia WGS AF: 0.395 AC: 1291 AN: 3270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.35
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28687962; hg19: chr17-203531; COSMIC: COSV58739034;