rs2201840

chr15-24899980-A-Gchr15-24899980-A-T

Variant summary

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

The ENST00000400097.5(SNRPN):c.-505+13391A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,142 control chromosomes in the GnomAD database, including 51,591 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 0.82 (51591 hom., cov: 32)
• Consequence: SNRPN ENST00000400097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.50

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=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNHG14	NR_146177.1	n.398+13391A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPN	ENST00000400097.5	c.-505+13391A>G		intron_variant		1		P1
SNRPN	ENST00000400100.5	c.-505+13391A>G		intron_variant		1		P1
SNRPN	ENST00000642807.1	c.-693+13391A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124543 AN: 152024 Hom.: 51550 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.813

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

GnomAD4 genome AF: 0.819 AC: 124642 AN: 152142 Hom.: 51591 Cov.: 32 AF XY: 0.821 AC XY: 61060 AN XY: 74350

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.815

Alfa AF: 0.772 Hom.: 61431

Bravo AF: 0.818

Asia WGS AF: 0.879 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.36
Dann	Benign	0.36

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: rs2201840; hg19: chr15-25145127;