ENST00000400097.5:c.-390-7493T>C

Variant names:

• chr15-24954621-T-C
• rs220030
• ENST00000400097.5:c.-390-7493T>C

Variant summary

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

The ENST00000400097.5(SNRPN):​c.-390-7493T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,136 control chromosomes in the GnomAD database, including 8,906 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 0.34 (8906 hom., cov: 33)
• Consequence: SNRPN ENST00000400097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 20 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]

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 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.-548-7493T>C		intron	N/A	NP_001365180.1
	SNRPN	NM_001349454.2		c.-370-4117T>C		intron	N/A	NP_001336383.1
	SNRPN	NM_001349455.2		c.-390-7493T>C		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.-390-7493T>C		intron	N/A	ENSP00000382969.1
	SNRPN	ENST00000400100.5	TSL:1	c.-390-7493T>C		intron	N/A	ENSP00000382972.1
	SNRPN	ENST00000642807.1		c.-390-7493T>C		intron	N/A	ENSP00000495345.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50981 AN: 152018 Hom.: 8894 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.335 AC: 51005 AN: 152136 Hom.: 8906 Cov.: 33 AF XY: 0.332 AC XY: 24686 AN XY: 74382

African (AFR) AF: 0.274 AC: 11366 AN: 41498

American (AMR) AF: 0.420 AC: 6416 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2639 AN: 5168

South Asian (SAS) AF: 0.165 AC: 796 AN: 4832

European-Finnish (FIN) AF: 0.304 AC: 3209 AN: 10570

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24092 AN: 67994

Other (OTH) AF: 0.341 AC: 719 AN: 2110

Alfa AF: 0.350 Hom.: 16132

Bravo AF: 0.349

Asia WGS AF: 0.320 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.40
PhyloP100		0.033
PromoterAI		0.0062	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs220030; hg19: chr15-25199768;