rs11869174

chr17-348907-T-Cchr17-348907-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006987.4(RPH3AL):c.-213+3805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,146 control chromosomes in the GnomAD database, including 3,639 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 0.21 (3638 hom., cov: 32)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: RPH3AL NM_006987.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPH3AL	NM_006987.4	c.-213+3805A>G		intron_variant		ENST00000331302.12
RPH3AL	NM_001190411.2	c.-37+3805A>G		intron_variant
RPH3AL	NM_001190412.2	c.-213+3805A>G		intron_variant
RPH3AL	NM_001190413.2	c.-37+3805A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPH3AL	ENST00000331302.12	c.-213+3805A>G		intron_variant		2	NM_006987.4	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32037 AN: 152016 Hom.: 3637 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.400 AC: 4 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.211 AC: 32056 AN: 152136 Hom.: 3638 Cov.: 32 AF XY: 0.204 AC XY: 15145 AN XY: 74376

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.217

Alfa AF: 0.250 Hom.: 5851

Bravo AF: 0.208

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	4.1
Dann	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs11869174; hg19: chr17-198698; COSMIC: COSV58747351; COSMIC: COSV58747351;