rs2201840

Variant names:

• chr15-24899980-A-G
• rs2201840
• ENST00000400097.5:c.-505+13391A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-24899980-A-G
• chr15-24899980-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000286110 (HGNC:):

SNHG14 (HGNC:37462): (small nucleolar RNA host gene 14) This gene is located within the Prader-Willi critical region and produces a long, spliced paternally-imprinted RNA that initiates within a common upstream promoter region shared by the SNRPN (small nuclear ribonucleoprotein polypeptide N) and SNURF genes. This transcript serves as a host RNA for the small nucleolar RNA, C/D box 115 and 116 clusters. This RNA extends in antisense into the region of the ubiquitin protein ligase E3A gene (UBE3A), and is thought to regulate imprinted expression of UBE3A in the brain. This transcript undergoes extensive alternative splicing, and may initiate and terminate at multiple locations within this genomic region. The full-length structure of all splice forms is not determined. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000400097.5. 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
	SNRPN	NM_001378251.1		c.-738+13391A>G		intron	N/A	NP_001365180.1
	SNRPN	NM_001349454.2		c.-727-12383A>G		intron	N/A	NP_001336383.1
	SNRPN	NM_001349455.2		c.-672-12383A>G		intron	N/A	NP_001336384.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPN	ENST00000400097.5	TSL:1	c.-505+13391A>G		intron	N/A	ENSP00000382969.1
	SNRPN	ENST00000400100.5	TSL:1	c.-505+13391A>G		intron	N/A	ENSP00000382972.1
	SNRPN	ENST00000642807.1		c.-693+13391A>G		intron	N/A	ENSP00000495345.1

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

African (AFR) AF: 0.925 AC: 38408 AN: 41540

American (AMR) AF: 0.756 AC: 11528 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2857 AN: 3468

East Asian (EAS) AF: 0.986 AC: 5088 AN: 5162

South Asian (SAS) AF: 0.810 AC: 3906 AN: 4824

European-Finnish (FIN) AF: 0.829 AC: 8771 AN: 10576

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51384 AN: 67998

Other (OTH) AF: 0.815 AC: 1722 AN: 2112

Alfa AF: 0.778 Hom.: 86651

Bravo AF: 0.818

Asia WGS AF: 0.879 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.36
DANN	Benign	0.36
PhyloP100		-4.5
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: rs2201840; hg19: chr15-25145127;