dbSNP rs4985615: RPH3AL:c.78-1144C>G (chr17-322559-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.87

Publications

1 publications found

Variant links:

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 links:

ENSG00000262920 (HGNC:58550):

ENSG00000262920 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RPH3AL	NM_006987.4 link	c.78-1144C>G	intron_variant	Intron 3 of 9	ENST00000331302.12	NP_008918.1
RPH3AL	NM_001190411.2 link	c.78-1144C>G	intron_variant	Intron 2 of 8		NP_001177340.1
RPH3AL	NM_001190412.2 link	c.78-1144C>G	intron_variant	Intron 3 of 8		NP_001177341.1
RPH3AL	NM_001190413.2 link	c.78-1144C>G	intron_variant	Intron 2 of 7		NP_001177342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPH3AL	ENST00000331302.12 link	c.78-1144C>G		intron_variant	Intron 3 of 9	2	NM_006987.4	ENSP00000328977.7

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46100

AN:

151890

Hom.:

7099

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.300

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.303

AC:

46116

AN:

152008

Hom.:

7099

Cov.:

AF XY:

0.305

AC XY:

22646

AN XY:

74288

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1649

3299

4948

6598

8247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.34

(source)

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)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over