15-24829910-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000400100.5(SNRPN):c.-579+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,030 control chromosomes in the GnomAD database, including 1,495 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1494 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: SNRPN ENST00000400100.5 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 0.00002453
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 15-24829910-G-A is Benign according to our data. Variant chr15-24829910-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 315435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNHG14	NR_146177.1	n.324+5G>A		splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPN	ENST00000400100.5	c.-579+5G>A		splice_donor_5th_base_variant, intron_variant		1		P1
SNRPN	ENST00000642807.1	c.-767+5G>A		splice_donor_5th_base_variant, intron_variant				P1
SNRPN	ENST00000645002.1	c.-878+5G>A		splice_donor_5th_base_variant, intron_variant				P1
SNRPN	ENST00000400098.6	n.187+6087G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19659 AN: 151800 Hom.: 1485 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.152 AC: 17 AN: 112 Hom.: 1 Cov.: 0 AF XY: 0.161 AC XY: 10 AN XY: 62

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.0833

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.130 AC: 19678 AN: 151918 Hom.: 1494 Cov.: 32 AF XY: 0.130 AC XY: 9653 AN XY: 74232

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0271

Gnomad4 SAS AF: 0.0519

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0705 Hom.: 101

Bravo AF: 0.129

Asia WGS AF: 0.0470 AC: 168 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism spectrum disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.013
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.70		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.70		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56684653; hg19: chr15-25075057;