rs4985611

Variant names:

• chr17-353554-A-C
• rs4985611
• ENST00000907490.1:c.-154-4179T>G

Variant summary

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

The ENST00000573780.5(RPH3AL):​c.-36-25975T>G variant causes a intron 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 0.83 (24772 hom., cov: 0)
• Consequence: RPH3AL ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 1 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]

RPH3AL-AS2 (HGNC:56089): (RPH3AL antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000573780.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	ENST00000907490.1		c.-154-4179T>G		intron	N/A	ENSP00000577549.1
	RPH3AL	ENST00000907489.1		c.-36-25975T>G		intron	N/A	ENSP00000577548.1
	RPH3AL	ENST00000913661.1		c.-153-25726T>G		intron	N/A	ENSP00000583720.1

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

African (AFR) AF: 0.799 AC: 20337 AN: 25456

American (AMR) AF: 0.839 AC: 5017 AN: 5980

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 1239 AN: 1452

East Asian (EAS) AF: 0.720 AC: 2360 AN: 3278

South Asian (SAS) AF: 0.765 AC: 1318 AN: 1722

European-Finnish (FIN) AF: 0.869 AC: 4211 AN: 4846

Middle Eastern (MID) AF: 0.855 AC: 106 AN: 124

European-Non Finnish (NFE) AF: 0.852 AC: 22693 AN: 26642

Other (OTH) AF: 0.888 AC: 810 AN: 912

Alfa AF: 0.956 Hom.: 5431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.49
PhyloP100		-2.1
PromoterAI		0.022	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4985611;

hg19: chr17-203345;