chr15-24920629-A-G

Variant names:

• chr15-24920629-A-G
• rs2075814
• ENST00000400097.5:c.-391+505A>G

Variant summary

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

The ENST00000400097.5(SNRPN):​c.-391+505A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,196 control chromosomes in the GnomAD database, including 992 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 0.10 (992 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: SNRPN ENST00000400097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 8 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 = 0.309 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.-549+82A>G		intron	N/A	NP_001365180.1
	SNRPN	NM_001349454.2		c.-371+82A>G		intron	N/A	NP_001336383.1
	SNRPN	NM_001349455.2		c.-391+505A>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.-391+505A>G		intron	N/A	ENSP00000382969.1
	SNRPN	ENST00000400100.5	TSL:1	c.-391+505A>G		intron	N/A	ENSP00000382972.1
	SNRPN	ENST00000642807.1		c.-579+505A>G		intron	N/A	ENSP00000495345.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15600 AN: 152052 Hom.: 996 Cov.: 32

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0417 AC: 1 AN: 24 Hom.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0500 AC: 1 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.102 AC: 15586 AN: 152172 Hom.: 992 Cov.: 32 AF XY: 0.103 AC XY: 7660 AN XY: 74390

African (AFR) AF: 0.0513 AC: 2132 AN: 41542

American (AMR) AF: 0.0995 AC: 1520 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 571 AN: 3472

East Asian (EAS) AF: 0.322 AC: 1652 AN: 5128

South Asian (SAS) AF: 0.100 AC: 482 AN: 4822

European-Finnish (FIN) AF: 0.0960 AC: 1017 AN: 10596

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7743 AN: 68010

Other (OTH) AF: 0.112 AC: 237 AN: 2114

Alfa AF: 0.113 Hom.: 1848

Bravo AF: 0.105

Asia WGS AF: 0.183 AC: 635 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	1.7
DANN	Benign	0.29
PhyloP100		-0.34
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: rs2075814; hg19: chr15-25165776;