rs2030062

chr15-24888839-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000400097.5(SNRPN):c.-505+2250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,206 control chromosomes in the GnomAD database, including 3,384 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 0.20 (3384 hom., cov: 33)
• Consequence: SNRPN ENST00000400097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502

Genes affected

SNRPN (HGNC:11164): (small nuclear ribonucleoprotein polypeptide N) This gene is located within the Prader-Willi Syndrome critical region on chromosome 15 and is imprinted and expressed from the paternal allele. It encodes a component of the small nuclear ribonucleoprotein complex, which functions in pre-mRNA processing and may contribute to tissue-specific alternative splicing. Alternative promoter use and alternative splicing result in a multitude of transcript variants encoding the same protein. Transcript variants that initiate at the CpG island-associated imprinting center may be bicistronic and also encode the SNRPN upstream reading frame protein (SNURF) from an upstream open reading frame. In addition, long spliced transcripts for small nucleolar RNA host gene 14 (SNHG14) may originate from the promoters at this locus and share exons with this gene. Alterations in this region are associated with parental imprint switch failure, which may cause Angelman syndrome or Prader-Willi syndrome. [provided by RefSeq, Mar 2017]

SNHG14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNHG14	NR_146177.1	n.398+2250A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPN	ENST00000400097.5	c.-505+2250A>G		intron_variant		1		P1
SNRPN	ENST00000400100.5	c.-505+2250A>G		intron_variant		1		P1
SNRPN	ENST00000642807.1	c.-693+2250A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30379 AN: 152088 Hom.: 3385 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.200 AC: 30396 AN: 152206 Hom.: 3384 Cov.: 33 AF XY: 0.204 AC XY: 15209 AN XY: 74396

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.00926

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.195

Alfa AF: 0.212 Hom.: 4556

Bravo AF: 0.181

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	13
Dann	Benign	0.64

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: rs2030062; hg19: chr15-25133986;