17-353214-A-G

Variant names:

• chr17-353214-A-G
• rs7223403
• ENST00000907490.1:c.-154-3839T>C

Variant summary

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

The ENST00000573780.5(RPH3AL):​c.-36-25635T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 152,086 control chromosomes in the GnomAD database, including 71,194 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 0.97 (71184 hom., cov: 30)
  • Exomes 𝑓: 1.0 (10 hom.)
• Consequence: RPH3AL ENST00000573780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.-154-3839T>C		intron	N/A	ENSP00000577549.1
	RPH3AL	ENST00000907489.1		c.-36-25635T>C		intron	N/A	ENSP00000577548.1
	RPH3AL	ENST00000913661.1		c.-153-25386T>C		intron	N/A	ENSP00000583720.1

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146833 AN: 151948 Hom.: 71135 Cov.: 30

Gnomad AFR AF: 0.886

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.976

GnomAD4 exome AF: 1.00 AC: 20 AN: 20 Hom.: 10 AF XY: 1.00 AC XY: 10 AN XY: 10

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: 1.00 AC: 8 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 10 AN: 10

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.966 AC: 146942 AN: 152066 Hom.: 71184 Cov.: 30 AF XY: 0.967 AC XY: 71861 AN XY: 74330

African (AFR) AF: 0.886 AC: 36726 AN: 41458

American (AMR) AF: 0.985 AC: 15048 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 3399 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5138 AN: 5138

South Asian (SAS) AF: 0.999 AC: 4813 AN: 4816

European-Finnish (FIN) AF: 1.00 AC: 10582 AN: 10582

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67973 AN: 68010

Other (OTH) AF: 0.976 AC: 2059 AN: 2110

Alfa AF: 0.992 Hom.: 3493

Bravo AF: 0.961

Asia WGS AF: 0.992 AC: 3450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.31
PhyloP100		-1.1
PromoterAI		0.044	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: rs7223403;

hg19: chr17-203005;