rs11356209

chr17-353541-CA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000572499.1(RPH3AL-AS2):n.225+680del 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 0.533 in 54,770 control chromosomes in the GnomAD database, including 7,236 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (7236 hom., cov: 0)
• Consequence: RPH3AL-AS2 ENST00000572499.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 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+680del		intron_variant, non_coding_transcript_variant		3
RPH3AL	ENST00000573780.5	c.-36-25963del		intron_variant		4
RPH3AL	ENST00000575130.5	c.-212-19608del		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.533 AC: 29132 AN: 54690 Hom.: 7229 Cov.: 0

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.533 AC: 29175 AN: 54770 Hom.: 7236 Cov.: 0 AF XY: 0.543 AC XY: 14748 AN XY: 27144

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11356209; hg19: chr17-203332; COSMIC: COSV58738462;