rs2732020

Variant names:

• chr15-24977157-C-A
• rs2732020
• NM_003097.6:c.420+128C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-24977157-C-A
• chr15-24977157-C-G
• chr15-24977157-C-T

Variant summary

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

The NM_003097.6(SNRPN):​c.420+128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 647,886 control chromosomes in the GnomAD database, including 4,739 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 0.14 (2437 hom., cov: 32)
  • Exomes 𝑓: 0.085 (2302 hom.)
• Consequence: SNRPN NM_003097.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• 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]

ENSG00000214265 (HGNC:):

SNURF (HGNC:11171): (SNRPN upstream open reading frame) This gene is located within the Prader-Willi Syndrome critical region on chromosome 15. Transcripts produced from this gene initiate at an imprinting center and are paternally-imprinted. These transcripts may be bicistronic and also encode SNRPN (small nuclear ribonucleoprotein polypeptide N) from a downstream open reading frame. The small protein represented by this gene is encoded by an evolutionarily-conserved upstream open reading frame and is localized to the nucleus. Extensive alternative splicing and promoter usage occurs in this region and the full-length nature of some of these transcripts has not been determined. Alterations in the imprinting center 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 (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPN	NM_003097.6	c.420+128C>A		intron_variant	Intron 7 of 9	ENST00000390687.9	NP_003088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPN	ENST00000390687.9	c.420+128C>A		intron_variant	Intron 7 of 9	1	NM_003097.6	ENSP00000375105.4
ENSG00000214265	ENST00000551312.6	n.*46-2379C>A		intron_variant	Intron 3 of 7	5		ENSP00000451421.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21887 AN: 151964 Hom.: 2421 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0810

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0899

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.0854 AC: 42333 AN: 495804 Hom.: 2302 AF XY: 0.0837 AC XY: 20955 AN XY: 250368

African (AFR) AF: 0.309 AC: 3432 AN: 11096

American (AMR) AF: 0.0619 AC: 600 AN: 9694

Ashkenazi Jewish (ASJ) AF: 0.0361 AC: 451 AN: 12510

East Asian (EAS) AF: 0.00347 AC: 86 AN: 24780

South Asian (SAS) AF: 0.0557 AC: 1428 AN: 25622

European-Finnish (FIN) AF: 0.0946 AC: 3167 AN: 33490

Middle Eastern (MID) AF: 0.0568 AC: 118 AN: 2076

European-Non Finnish (NFE) AF: 0.0878 AC: 30725 AN: 350104

Other (OTH) AF: 0.0880 AC: 2326 AN: 26432

GnomAD4 genome AF: 0.144 AC: 21943 AN: 152082 Hom.: 2437 Cov.: 32 AF XY: 0.141 AC XY: 10478 AN XY: 74368

African (AFR) AF: 0.314 AC: 13005 AN: 41432

American (AMR) AF: 0.0808 AC: 1235 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5174

South Asian (SAS) AF: 0.0573 AC: 276 AN: 4820

European-Finnish (FIN) AF: 0.0899 AC: 952 AN: 10590

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0881 AC: 5986 AN: 67984

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.102 Hom.: 1584

Bravo AF: 0.150

Asia WGS AF: 0.0560 AC: 194 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	0.24
DANN	Benign	0.38
PhyloP100		-0.55
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: rs2732020; hg19: chr15-25222304;