rs12949751

Positions:

• chr17-353709-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000572499.1(RPH3AL-AS2):​n.225+847G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. 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 0.00028 (0 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: RPH3AL-AS2 ENST00000572499.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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+847G>A		intron_variant, non_coding_transcript_variant		3
RPH3AL	ENST00000573780.5	c.-36-26130C>T		intron_variant		4		ENSP00000459992
RPH3AL	ENST00000575130.5	c.-212-19775C>T		intron_variant		4		ENSP00000460171

Frequencies

GnomAD3 genomes AF: 0.00 AC: 26 AN: 94308 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.0000642

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000121

Gnomad ASJ AF: 0.000513

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000799

Gnomad FIN AF: 0.000312

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000479

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000275 AC: 26 AN: 94424 Hom.: 0 Cov.: 29 AF XY: 0.000479 AC XY: 22 AN XY: 45974

Gnomad4 AFR AF: 0.0000639

Gnomad4 AMR AF: 0.000121

Gnomad4 ASJ AF: 0.000513

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000800

Gnomad4 FIN AF: 0.000312

Gnomad4 NFE AF: 0.000479

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12949751; hg19: chr17-203500;