rs4985611

chr17-353554-A-C

Variant summary

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

The ENST00000572499.1(RPH3AL-AS2):n.225+692A>C 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 0.825 in 70,714 control chromosomes in the GnomAD database, including 24,772 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 0.83 (24772 hom., cov: 0)
• Consequence: RPH3AL-AS2 ENST00000572499.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 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+692A>C		intron_variant, non_coding_transcript_variant		3
RPH3AL	ENST00000573780.5	c.-36-25975T>G		intron_variant		4
RPH3AL	ENST00000575130.5	c.-212-19620T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.825 AC: 58287 AN: 70624 Hom.: 24753 Cov.: 0

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.853

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.888

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

GnomAD4 genome AF: 0.825 AC: 58351 AN: 70714 Hom.: 24772 Cov.: 0 AF XY: 0.825 AC XY: 28745 AN XY: 34836

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.852

Gnomad4 OTH AF: 0.888

Alfa AF: 0.956 Hom.: 5431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.18
Dann	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4985611; hg19: chr17-203345;