17-353740-G-T

Variant names:

• chr17-353740-G-T
• rs28687962
• ENST00000717666.1:n.1127G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000717666.1(RPH3AL-AS2):​n.1127G>T variant causes a non coding transcript exon 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 ENST00000717666.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL-AS2	ENST00000717666.1	n.1127G>T		non_coding_transcript_exon_variant	Exon 1 of 2
RPH3AL	ENST00000573780.5	c.-36-26161C>A		intron_variant	Intron 1 of 4	4		ENSP00000459992.1
RPH3AL	ENST00000575130.5	c.-212-19806C>A		intron_variant	Intron 1 of 4	4		ENSP00000460171.1

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

African (AFR) AF: 0.413 AC: 14768 AN: 35792

American (AMR) AF: 0.281 AC: 3313 AN: 11774

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 806 AN: 2722

East Asian (EAS) AF: 0.622 AC: 2694 AN: 4330

South Asian (SAS) AF: 0.333 AC: 1234 AN: 3702

European-Finnish (FIN) AF: 0.378 AC: 3169 AN: 8380

Middle Eastern (MID) AF: 0.386 AC: 88 AN: 228

European-Non Finnish (NFE) AF: 0.260 AC: 14186 AN: 54516

Other (OTH) AF: 0.293 AC: 507 AN: 1730

Alfa AF: 0.284 Hom.: 1995

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
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs28687962; hg19: chr17-203531; COSMIC: COSV58739034;