17-353214-A-G

Position:

• chr17-353214-A-G

Variant summary

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

The ENST00000572499.1(RPH3AL-AS2):​n.225+352A>G 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 0.966 in 152,086 control chromosomes in the GnomAD database, including 71,194 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 0.97 (71184 hom., cov: 30)
  • Exomes 𝑓: 1.0 (10 hom.)
• Consequence: RPH3AL-AS2 ENST00000572499.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPH3AL-AS2	ENST00000572499.1	n.225+352A>G		intron_variant, non_coding_transcript_variant		3
RPH3AL	ENST00000573780.5	c.-36-25635T>C		intron_variant		4		ENSP00000459992
RPH3AL	ENST00000575130.5	c.-212-19280T>C		intron_variant		4		ENSP00000460171

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146833 AN: 151948 Hom.: 71135 Cov.: 30

Gnomad AFR AF: 0.886

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.976

GnomAD4 exome AF: 1.00 AC: 20 AN: 20 Hom.: 10 AF XY: 1.00 AC XY: 10 AN XY: 10

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.966 AC: 146942 AN: 152066 Hom.: 71184 Cov.: 30 AF XY: 0.967 AC XY: 71861 AN XY: 74330

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.985

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.976

Alfa AF: 0.992 Hom.: 3493

Bravo AF: 0.961

Asia WGS AF: 0.992 AC: 3450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7223403; hg19: chr17-203005;