rs7164989

Variant names:

• chr15-24852080-A-G
• rs7164989
• ENST00000400100.5:c.-579+22175A>G

Variant summary

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

The ENST00000400100.5(SNRPN):​c.-579+22175A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,012 control chromosomes in the GnomAD database, including 15,891 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 0.43 (15891 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SNRPN ENST00000400100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756
• Publications: 12 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]

ENSG00000280118 (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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPN	NM_001378251.1	c.-812+22175A>G		intron_variant	Intron 2 of 13		NP_001365180.1
SNRPN	NM_001349455.2	c.-747+28257A>G		intron_variant	Intron 1 of 12		NP_001336384.1
SNRPN	NM_001349456.2	c.-654+28257A>G		intron_variant	Intron 1 of 12		NP_001336385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPN	ENST00000400100.5	c.-579+22175A>G		intron_variant	Intron 2 of 12	1		ENSP00000382972.1
ENSG00000280118	ENST00000623426.1	n.3724A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000280118	ENST00000648546.3	n.654A>G		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65037 AN: 151892 Hom.: 15887 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.450

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.428 AC: 65048 AN: 152012 Hom.: 15891 Cov.: 33 AF XY: 0.428 AC XY: 31804 AN XY: 74284

African (AFR) AF: 0.169 AC: 7014 AN: 41482

American (AMR) AF: 0.494 AC: 7539 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2538 AN: 5156

South Asian (SAS) AF: 0.461 AC: 2223 AN: 4820

European-Finnish (FIN) AF: 0.526 AC: 5550 AN: 10544

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36936 AN: 67960

Other (OTH) AF: 0.449 AC: 944 AN: 2104

Alfa AF: 0.507 Hom.: 36717

Bravo AF: 0.416

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.2
DANN	Benign	0.43
PhyloP100		0.76
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: rs7164989; hg19: chr15-25097227;