17-353740-G-T

Position:

• chr17-353740-G-T

Variant summary

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

The ENST00000572499.1(RPH3AL-AS2):​n.225+878G>T 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 0.33 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-AS2 ENST00000572499.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.94).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3AL-AS2	ENST00000572499.1	n.225+878G>T		intron_variant, non_coding_transcript_variant		3
RPH3AL	ENST00000573780.5	c.-36-26161C>A		intron_variant		4
RPH3AL	ENST00000575130.5	c.-212-19806C>A		intron_variant		4

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;