rs11869174

Variant names:

• chr17-348907-T-C
• rs11869174
• NM_006987.4:c.-213+3805A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-348907-T-C
• chr17-348907-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	NM_006987.4	MANE Select	c.-213+3805A>G		intron	N/A	NP_008918.1
	RPH3AL	NM_001190411.2		c.-37+3805A>G		intron	N/A	NP_001177340.1
	RPH3AL	NM_001190412.2		c.-213+3805A>G		intron	N/A	NP_001177341.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPH3AL	ENST00000331302.12	TSL:2 MANE Select	c.-213+3805A>G		intron	N/A	ENSP00000328977.7
	RPH3AL	ENST00000323434.12	TSL:1	c.-213+3805A>G		intron	N/A	ENSP00000319210.8
	RPH3AL	ENST00000618002.4	TSL:5	c.-37+3805A>G		intron	N/A	ENSP00000479485.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.375 AC: 3 AN: 8

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

African (AFR) AF: 0.167 AC: 6935 AN: 41498

American (AMR) AF: 0.157 AC: 2400 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 896 AN: 3468

East Asian (EAS) AF: 0.142 AC: 732 AN: 5162

South Asian (SAS) AF: 0.140 AC: 673 AN: 4824

European-Finnish (FIN) AF: 0.207 AC: 2195 AN: 10582

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17525 AN: 67992

Other (OTH) AF: 0.217 AC: 458 AN: 2112

Alfa AF: 0.247 Hom.: 8327

Bravo AF: 0.208

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	4.1
DANN	Benign	0.68
PhyloP100		0.081
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: rs11869174; hg19: chr17-198698; COSMIC: COSV58747351; COSMIC: COSV58747351;