rs4617924

Variant names:

• chr17-264878-C-A
• rs4617924
• NM_006987.4:c.438+16890G>T

Variant summary

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

The NM_006987.4(RPH3AL):​c.438+16890G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,034 control chromosomes in the GnomAD database, including 19,590 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 0.51 (19590 hom., cov: 33)
• Consequence: RPH3AL NM_006987.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 14 publications found

Genes affected

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006987.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	NM_006987.4	MANE Select	c.438+16890G>T		intron	N/A	NP_008918.1
	RPH3AL	NM_001190411.2		c.438+16890G>T		intron	N/A	NP_001177340.1
	RPH3AL	NM_001190412.2		c.352-17593G>T		intron	N/A	NP_001177341.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	ENST00000331302.12	TSL:2 MANE Select	c.438+16890G>T		intron	N/A	ENSP00000328977.7
	RPH3AL	ENST00000323434.12	TSL:1	c.352-17593G>T		intron	N/A	ENSP00000319210.8
	RPH3AL	ENST00000953554.1		c.438+16890G>T		intron	N/A	ENSP00000623613.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76891 AN: 151914 Hom.: 19561 Cov.: 33

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.506 AC: 76963 AN: 152034 Hom.: 19590 Cov.: 33 AF XY: 0.509 AC XY: 37855 AN XY: 74324

African (AFR) AF: 0.505 AC: 20927 AN: 41426

American (AMR) AF: 0.509 AC: 7775 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1791 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3399 AN: 5182

South Asian (SAS) AF: 0.684 AC: 3301 AN: 4826

European-Finnish (FIN) AF: 0.495 AC: 5229 AN: 10566

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32750 AN: 67972

Other (OTH) AF: 0.533 AC: 1124 AN: 2110

Alfa AF: 0.495 Hom.: 75126

Bravo AF: 0.506

Asia WGS AF: 0.617 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.5
DANN	Benign	0.59
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4617924; hg19: chr17-114669; COSMIC: COSV58747190;