rs4985615

Variant names:

• chr17-322559-G-C
• rs4985615
• NM_006987.4:c.78-1144C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-322559-G-C
• chr17-322559-G-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.78-1144C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,034 control chromosomes in the GnomAD database, including 7,099 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 0.30 (7099 hom., cov: 32)
  • Exomes 𝑓: 0.23 (0 hom.)
• Consequence: RPH3AL NM_006987.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• 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]

ENSG00000262920 (HGNC:58550):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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.78-1144C>G		intron	N/A	NP_008918.1	Q9UNE2-1
	RPH3AL	NM_001190411.2		c.78-1144C>G		intron	N/A	NP_001177340.1	Q9UNE2-1
	RPH3AL	NM_001190412.2		c.78-1144C>G		intron	N/A	NP_001177341.1	Q9UNE2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	ENST00000331302.12	TSL:2 MANE Select	c.78-1144C>G		intron	N/A	ENSP00000328977.7	Q9UNE2-1
	RPH3AL	ENST00000323434.12	TSL:1	c.78-1144C>G		intron	N/A	ENSP00000319210.8	Q9UNE2-2
	RPH3AL	ENST00000953554.1		c.78-1144C>G		intron	N/A	ENSP00000623613.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46100 AN: 151890 Hom.: 7099 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.231 AC: 6 AN: 26 Hom.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.300 AC: 6 AN: 20

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.303 AC: 46116 AN: 152008 Hom.: 7099 Cov.: 32 AF XY: 0.305 AC XY: 22646 AN XY: 74288

African (AFR) AF: 0.316 AC: 13106 AN: 41458

American (AMR) AF: 0.323 AC: 4928 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 923 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2214 AN: 5160

South Asian (SAS) AF: 0.315 AC: 1513 AN: 4802

European-Finnish (FIN) AF: 0.264 AC: 2796 AN: 10576

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19584 AN: 67954

Other (OTH) AF: 0.294 AC: 620 AN: 2112

Alfa AF: 0.166 Hom.: 321

Bravo AF: 0.309

Asia WGS AF: 0.390 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.57
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4985615; hg19: chr17-172350;